1. Fetal Circulation (Image 1 - yellow board)

• Red vessels = oxygenated blood; Blue vessels = deoxygenated blood
• Pathway: Oxygenated blood from the placenta travels via the umbilical vein → ~50% bypasses the liver through the ductus venosus → inferior vena cava (IVC) → right atrium → most crosses through the foramen ovale into the left atrium (guided by the crista dividens) → left ventricle → ascending aorta to supply the heart and brain with the best-oxygenated blood
• Deoxygenated blood from the SVC → right ventricle → pulmonary trunk → ductus arteriosus (bypasses the high-resistance fetal lungs) → descending aorta → two umbilical arteries back to the placenta

1. Ductus venosus - bypasses the liver
2. Foramen ovale - bypasses the lungs (right atrium → left atrium)
3. Ductus arteriosus - bypasses the lungs (pulmonary trunk → aorta)

2 & 3. Heart Models (Images 2 & 3 - red/blue model on stand)

• Red = right side (arteries/aorta) and left-sided structures
• Blue = venous/pulmonary structures (SVC, IVC, pulmonary veins entering the left atrium)
• Visible structures: aorta (arching over the top), pulmonary trunk (blue, left side), superior vena cava (blue, right), coronary vessels on the surface of the ventricles
• The model shows the characteristic relationship of the great vessels: aorta is posterior/rightward, pulmonary trunk is anterior/leftward

4. Folding of Heart Tube (Image 4 - brown bulging model)

• The primitive heart tube (initially straight) undergoes a rightward bend called the D-loop (dextral looping) around day 23-28 of development
• The looping brings the future ventricles inferiorly and anteriorly, and the atria posteriorly and superiorly
• The constrictions/bulgings represent the five segments of the primitive heart tube: truncus arteriosus → bulbus cordis → primitive ventricle → primitive atrium → sinus venosus
• Failure of normal D-loop gives situs inversus or congenital heart defects

5. Numbered Model (Image 5 - orange/blue/dark structure)

• 1 (orange, top) = likely truncus arteriosus or early aortic sac
• 2 (blue, side) = aortic arch vessel
• 3 (orange, lower) = bulbus cordis
• 4, 4 (dark blue, bilateral) = vitelline veins or early atrial horns/sinus venosus components

6. Heart Tube (second brown folding model - Image 6 / unlabeled)

7. Development of Portal Vein (Image 8 - yellow board)

• Left panel (complex network): The paired vitelline veins originally form an extensive network of anastomoses around the developing duodenum - shown as the dense ladder-like pattern with the liver (brown blob) in the middle
• Right panels (simplified): Show progressive regression where parts of both veins disappear, leaving only specific segments. The portal vein forms from:
  • Cranial part of the right vitelline vein
  • Anastomotic channels around the duodenum
  • Caudal part of the left vitelline vein
• The red dots mark points of obliteration/regression
• The final portal vein is an asymmetric structure - this asymmetry explains why the portal vein lies posterior to the bile duct

8. Heart Tube (Image 9 - tall straight brown model labeled "HEART TUBE")

• The segmented bulges (top to bottom) represent: Aortic sac → Truncus arteriosus → Bulbus cordis → Primitive ventricle → Primitive atrium → Sinus venosus (the small horizontal projection at the base)
• This stage corresponds to approximately day 22-23 of embryonic development
• At this stage the heart is already beating (first organ to function) even before it has finished forming

9. Inter-Atrial Septum (Image 10 - brown, butterfly-like model)

• The upper curved wing = Septum primum - a crescent-shaped partition growing down from the roof of the primitive atrium toward the endocardial cushions
• The lower wing = Septum secundum - a thicker, muscular partition that grows to the right of septum primum, also descending from the atrial roof but leaving a permanent opening (the foramen ovale)
• The gap/hole visible between the two wings = the foramen ovale (in fetal life, the flap of septum primum acts as a one-way valve allowing blood flow from right to left atrium)
• At birth, increased left atrial pressure forces septum primum against septum secundum, functionally closing the foramen ovale; anatomical closure (forming the fossa ovalis) occurs within weeks
• Failure of closure = Patent Foramen Ovale (PFO), present in ~25% of adults

10. Aortic Arches (Image 10 - yellow board with red vessels)

• Left panel (complex symmetrical pattern): The original 6 pairs of pharyngeal arch arteries connecting the aortic sac to the paired dorsal aortae - arches 1-6 are all shown as symmetric loops
• Right panel (asymmetric adult pattern): Shows what persists after regression:
  • Arch 1, 2 - mostly disappear (remnants form maxillary artery, stapedial artery)
  • Arch 3 → common carotid and proximal internal carotid arteries
  • Arch 4 → aortic arch proper (left), right subclavian artery (right)
  • Arch 5 → disappears
  • Arch 6 → pulmonary arteries + ductus arteriosus (left side)
• The asymmetry between left and right is due to selective regression of specific arches on each side

Symbol Key (applies to both charts)

Chart 1 (Top) - X-Linked Recessive Inheritance

Generation-by-Generation Breakdown

• Father (I-1): Unaffected male → genotype X^A Y
• Mother (I-2): Carrier female (dot in circle) → genotype X^A X^a

• II-1: Carrier female ⊙ → X^A X^a
• II-2: Affected male ■ → X^a Y (received the faulty X from his carrier mother)
• II-3: Unaffected female ○ → X^A X^A (marries II-2)
• II-4: Unaffected male □ → X^A Y
• II-5: Unaffected female ○ → X^A X^A

• III-1: Unaffected male □ → X^A Y (got Y from affected father)
• III-2: Carrier female ⊙ → X^A X^a (got X^a from affected father)
• III-3: Unaffected male □ → X^A Y
• III-4: Carrier female ⊙ → X^A X^a

Why X-Linked Recessive?

1. Only males are affected - females can be carriers but not affected (they have two X chromosomes, so one normal copy masks the defective one)
2. Carrier mothers pass it to sons - I-2 (carrier) → II-2 (affected son)
3. Criss-cross inheritance - the affected father (II-2) passes his faulty X chromosome to ALL his daughters, making ALL daughters obligate carriers (III-2 and III-4 are both ⊙). He passes his Y to his sons, so no sons are affected
4. Trait skips generations in females (appears only in males in most generations)
5. Examples: Hemophilia A & B, Duchenne muscular dystrophy, red-green color blindness

Chart 2 (Bottom) - Autosomal Recessive Inheritance

Generation-by-Generation Breakdown

• Father (I-1): Half-shaded square → Carrier male (Aa)
• Mother (I-2): Half-shaded circle → Carrier female (Aa)

• II-1: Unaffected female ○ → AA or Aa
• II-2: Affected male ■ → aa (received recessive allele from both carrier parents)
• II-3: Unaffected female ○ → AA (marries II-2)
• II-4: Half-shaded male → Carrier (Aa)
• II-5: Half-shaded female → Carrier (Aa)

• All four children (III-1 to III-4) are half-shaded (two males, two females) → all obligate carriers (Aa)

Why Autosomal Recessive?

1. Both males AND females are carriers - rules out X-linked (males cannot be carriers in X-linked, they're either affected or normal)
2. Two carrier parents (Aa × Aa) → produced one affected child (aa) - classic 25% risk
3. Affected father (aa) × normal mother (AA) → 100% of children are carriers (Aa), which is exactly what Gen III shows (all four children are half-shaded)
4. Trait affects both sexes equally - no sex bias
5. Examples: Cystic fibrosis, sickle cell disease, PKU, albinism

Key Comparison

How to Read a Karyotype

• Example: 47,XY,+21 = male with trisomy 21

Karyotype 1 (Top Image) - 46,XX

What it shows:

• 46 chromosomes total
• 22 pairs of autosomes (pairs 1-22), all appearing as matched pairs - normal in number and structure
• Sex chromosomes: XX (two X chromosomes visible, no Y chromosome)

Interpretation: Normal Female Karyotype - 46,XX

• Pairs 1, 2, 3 - largest metacentric chromosomes (top row)
• Pairs 13, 14, 15, 21, 22 - acrocentric chromosomes with satellites (tiny knobs at the top - these carry ribosomal RNA genes)
• X chromosomes - medium-sized, pair shown at bottom right

Karyotype 2 (Bottom Image) - Abnormal Female

What it shows:

• The bottom karyotype is notably incomplete - several pairs in the smaller chromosome range (19, 20, 21, 22) appear to have only 1 chromosome instead of 2, or are missing entirely
• Sex chromosomes: XX (two X chromosomes present, no Y)
• Pairs 1-18 appear present as pairs

Interpretation: Incomplete/Artifact Karyotype - Technical Preparation Issue

1. Cells are treated with hypotonic solution to swell
2. Then fixed and dropped onto a slide - causing chromosomes to scatter
3. During this step, smaller chromosomes (pairs 19-22) can roll off the slide or drift away, since they are physically tiny and light

• How to recognise incomplete spreads
• The importance of counting all 46 chromosomes before reporting
• That at least 20 cells must be analysed and counted in clinical cytogenetics to confirm a result

Clinical Significance - Why Karyotyping Matters

Part 1 (Top Section) - Chromosome Structural Abnormalities

1. Normal Chromosome Pair (reference)

2. Deletion

• Terminal deletion = loss from the tip of an arm
• Interstitial deletion = loss from within the middle of an arm
• The remaining chromosome is shorter than its homolog
• Clinical example: Deletion of short arm of chromosome 5 → Cri du chat syndrome (cat-like cry, microcephaly, intellectual disability)

3. Inversion

• The chromosome looks structurally intact but gene order is reversed in the inverted segment
• Carriers are usually phenotypically normal but risk having offspring with unbalanced chromosomes due to abnormal crossing-over during meiosis

4. Isochromosome (top right - X-shaped)

• Results in two identical arms (either two p arms or two q arms)
• Most common: i(Xq) = isochromosome of long arm of X → seen in Turner syndrome variants
• The chromosome has the same genes duplicated on both arms and is missing the other arm entirely

5. Ring Chromosome (circle shape)

• The lost telomeric material causes gene loss
• Ring chromosomes are unstable during cell division - they can interlock and break further
• Found in Turner syndrome (ring X), trisomy 18 variants, and others
• Clinically: patients have features of partial deletion of whichever chromosome is involved

6. Translocation / Insertion (elongated chromosome pair)

• Reciprocal translocation: Two non-homologous chromosomes exchange segments with each other (balanced - no gain or loss)
• Robertsonian translocation: Two acrocentric chromosomes (13, 14, 15, 21, 22) fuse at their centromeres, losing their short arms → results in 45 chromosomes but balanced
  • Most common: Chromosome 14/21 fusion → carrier is normal but risk of translocation Down syndrome in offspring (3-4% of all Down syndrome cases)

Part 2 (Bottom Section) - Denver Classification Karyotype: 46,XY

Denver Classification Groups

Centromere Position Terminology

• Metacentric - centromere in the middle, equal arms (p = q)
• Submetacentric - centromere slightly off-center, arms unequal
• Acrocentric - centromere near one end, very short p arm; carry satellites (ribosomal RNA genes) on the short arm tips
• Telocentric - centromere at the very tip (not seen in humans normally)

Why Denver Classification Matters

Summary

Image 1 - Cleft Lip (Screen display, upside down)

Top photo (labeled A) - Median Cleft Lip

• A vertical midline cleft splitting the upper lip exactly down the centre into two equal halves
• The cleft extends from the vermilion border up toward the nasal columella
• Rare - results from failure of fusion of the two medial nasal prominences during week 5-7 of embryonic development
• Nostrils appear relatively symmetrical (unlike unilateral cleft)

Bottom photo - Unilateral Cleft Lip (Left-sided)

• A complete unilateral cleft on the left side of the upper lip extending up into the floor of the left nostril
• More common type - results from failure of the maxillary prominence to fuse with the medial nasal prominence on one side
• Causes characteristic nasal asymmetry: left nostril is flattened and flared, nasal septum/columella deviated away from the cleft side
• Incidence: ~1 in 700-1000 births; more common in males

Image 2 - Two Karyotypes (46,XY and 46,XX)

Top Karyotype: 46,XY - Normal Male

• 46 chromosomes total
• All 22 autosomal pairs present and normal
• Sex chromosomes: one X + one Y
• No trisomies, monosomies, or structural abnormalities

Bottom Karyotype: 46,XX - Normal Female

• 46 chromosomes total
• All 22 autosomal pairs present and normal
• Sex chromosomes: two X chromosomes, no Y
• No chromosomal abnormalities

Image 3 - Sex Chromatin (Barr Body & Drumstick)

Top Image - Drumstick (Davidson Body) in Neutrophil

• Peripheral blood smear stained with Leishman's/Wright's stain
• Background shows biconcave red blood cells (erythrocytes)
• The arrow points to a neutrophil (multi-lobed nucleus visible)
• The small drumstick-shaped nuclear appendage (~1.5 µm) attached by a thin chromatin thread to one nuclear lobe = Davidson body
• This is the sex chromatin (inactivated X chromosome) as it appears in neutrophils
• Found in ~3% of neutrophils in females; absent in males
• Named after Davidson and Smith (1954)

Bottom Image - Barr Body in Buccal Epithelial Cell

• Buccal (cheek) smear at high magnification
• Shows a single large buccal epithelial cell with prominent nucleus
• The arrow points to a Barr body - a small, densely-staining triangular/planoconvex mass of heterochromatin applied tightly to the inner surface of the nuclear membrane
• This is the condensed, inactivated X chromosome (Lyon hypothesis)
• Present in females (XX) - one Barr body per cell (number of Barr bodies = number of X chromosomes - 1)

Image 4 - Pedigree Symbol Key + Autosomal Dominant Pedigree

Top Section: Complete Pedigree Symbol Legend

Left column - Basic symbols & relationships:

Right column - Clinical status symbols:

Bottom Section: Pedigree Chart - Autosomal Dominant Inheritance

Generation by Generation:

• Father (I-1): Unaffected male □
• Mother (I-2): Affected female ● (filled)

• II-1: Affected female ●
• II-2: Affected male ■ (married to unaffected female II-3)
• II-3: Unaffected female ○
• II-4: Unaffected male □
• II-5: Unaffected female ○

• III-1: Unaffected male □
• III-2: Affected female ●
• III-3: Unaffected male □
• III-4: Affected female ●

Why Autosomal Dominant?

1. Trait appears in every generation - no generation is skipped (vertical transmission)
2. Both males and females are affected - not sex-limited (rules out Y-linked)
3. Affected parent × unaffected parent → ~50% of children affected (II-2 × II-3 → 2 affected, 2 unaffected = fits 1:1 ratio)
4. Unaffected individuals do not pass on the trait - II-4 and II-5 have no affected children shown
5. Genotypes: Affected individuals = Aa (heterozygous dominant); Unaffected = aa

• Huntington's disease
• Marfan syndrome
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• Neurofibromatosis type 1
• Polycystic kidney disease (adult type)