Case 1: Hannah Rosen Pt1

Gut Malrotation

Abnormal midgut rotation during embryogenesis = Improper fixing

Volvulus

Malrotated midgut torsion → Bowel ischemia + blockage

Protein Digestion

1. Stomach: Pepsin

2. Small Intestine: Pancreatic and brush-border proteases

• Endopeptidases: Hydrolyze peptide bonds

  • Pepsin

  • Trypsin

  • Chymotrypsin

  • Elastase

  Exopeptidases: Hydrolyze amino acids

  • Carboxypeptidases A/B

Protein Digestion: Pepsin

Chief cells secrete pepsinogen → Pepsin

• Activated by low pH from gastric H+

Neutralized in duodenum by high pH

Cleave peptide bonds = Proteins → Polypeptides and amino acids

Protein Digestion: Pancreatic + Brush-Border Proteases

Trypsinogen → Trypsin

• Enterokinase (brush-border enzyme)

Trypsinogen, chymotrypsinogen, proelastase, procarboxypeptidase A/B → Trypsin, chymotrypsin, elastase, carboxypeptidase A/B

• Trypsin

• Proteins → Oligopeptides, small peptides, amino acids

  • Oligopeptides → Small peptides + amino acids

Protein Absorption

As amino acids, dipeptides, and tripeptides

Protein Absorption: Amino Acids

Apical: Na+/amino acid cotransporter

• Energy from Na+ gradient

Basolateral: Facilitated diffusion

Protein Absorption: Peptides

Apical: H+-dependent cotransporters*

• Energy from H+ gradient by Na+/H+ exchanger

In Cell: Some peptides → Amino acids by cytosolic peptidases

Basolateral: Facilitated diffusion

Lipids

Triglycerides (TGA)

Cholesterol

Phospholipids

Lipid Digestion

1. Stomach: Lingual and gastric lipases

2. Small Intestine: Bile salts*** + pancreatic enzymes

• Pancreatic lipase

• Cholesterol ester hydrolase

• Phospholipase A2

Lipid Digestion: Lingual and Gastric Lipases

Mix lipids into droplets = Increase SA for enzymes

Lipases hydrolyze TGA → Glycerol + FFA

• Increased oxidative stress

Lipid Digestion: Bile Salts

Emulsify lipids in droplets = Increase SA

Lipid Digestion: Pancreatic Enzymes

Pancreatic Lipase: TGA → Monoglyceride + FFA

• Colipase prevent bile salts breaking down lipase

Cholesterol Ester Hydrolase: Cholesterol → Free cholesterol + FFA

Phospholipase A2: Phospholipids → Lysoleithin + FFA

• Activated by trypsin

Lipid Absorption

As monoglycerides, cholesterol, lysoleithin, FFA

Lipid Absorption: Process

1. Lumen: Lipid products → Micelles

• Hydrophobic centre (lipid products)

• Hydrophilic outer (bile salts)

2. Apical Membrane: Micelle transport lipid products

• Passive diffusion lipids → Cell

3. In Cell: Lipids packaged → Chylomicrons → Secretory vesicles

• Chylomicrons: Lipid centre + apoprotein outer

4. Basolateral Membrane: Secretory vesicles transport lipids

• Exocytosis

Carbs

Polysaccharides

Disaccharides (sucrose, lactose, maltose, trehalose)

Monosaccharides (glucose, fructose)

Carb Digestion

1. Mouth: a-amylase

2. Small Intestine: Pancreatic and brush-border enzymes

Carb Digestion: a-Amylase

Start starch digestion

Inactivated in stomach (low pH)

Carb Digestion: Pancreatic and Brush-Border Enzymes

Pancreatic Amylase: Starch → Disaccharides

Brush-Border Enzymes: a-Dextrinase, Maltase, Sucrase

• Disaccharides → Monosaccharides (glucose, galactose, fructose)

Carb Absorption

As monosaccharides (glucose, galactose, fructose)

Carb Absorption: Glucose + Galactose

Apical: Na+-glucose cotransporter (SGLT1)

• Energy from Na+ gradient by Na+/K+ ATPase

Basolateral: Facilitated diffusion (GLUT2)

Carb Absorption: Fructose

Facilitated diffusion

Apical: GLUT5

Basolateral: GLUT2

Water Absorption

Everywhere

Mostly in large intestines

Vit B12 Absorption

Terminal ileum

Nutrient Requirements: < 6 Months

Breast milk

• Contains:

  • Proteins

  • Lactose + oligosaccharides

  • Fats

  • Minerals

  • Trace elements (Fe, Cu, Zn, I, Se, S)

  • Vitamins

Fe-fortified formula supplementation

Nutrient Requirements: 6-11 Months

Breast milk/Fe-fortified formula

Introduce complementary foods

• Common allergens

• NO honey

Water

Nutrient Requirements: 12 Months

Breast milk (until ≥ 2 years)

• NO formula

Whole milk

Water

Growth

Physical measurement of size, weight, height, length

Development

Measurement of functional ability

Growth Charts

Height and weight on gender-specific chart

Compare to…

• Expected growth percentiles

• Mid-parental height (estimated adult height from parental height)

Growth Chart: Normal Growth

Follows percentile curve

Height within 2 SD of mid-parental height

Growth Chart: Abnormal Growth

Crossing ≥ 2 percentile lines

• > 2-3 years

< 3% or > 97% percentile

> 10cm from mid-parental height

Growth Relation to Feeding: Too High

High calorie intake

• Overfeeding

• Early complementary food intro (< 4 months)

Growth Relation to Feeding: Too Low

Low calorie intake

• Underfeeding

• Increased requirements (malignancy)

Decrease absorption

• Celiac

• IBD

• Allergies + intolerances

• CF

Decreased energy utilization

• Metabolism errors

• Genetic conditions

Wasting

Low weight for height

Acute malnutrition

Stunting

Low height for age

Chronic malnutrition

Autosomal Recessive: Pathogenic Mutation

Known to cause disease

Confirm diagnosis and guide management

Autosomal Recessive: Variant of Uncertain Significance (VUS)

Unknown if mutation is disease-causing or benign

No diagnostic confirmation

Autosomal Recessive: Risk to Relatives

Pathogenic Mutation: Increased risk

• Follow autosomal recessive inheritance pattern

VUS: Unknown risk

• Cannot conduct risk assessment

Cystic Fibrosis (CF): Description

Autosomal recessive disease impairing mucus hydration and clearance

CF: Epidemiology

Most prevalent in White people

Risk Factors:

• 2 carrier parents of transmembrane conductance regulator (CFTR) mutation

• Siblings with CF

CF: Etiology

CFTR mutation

Most common: ΔF508 phenylalanine deletion

> 2000 mutations

• 300 confirmed pathogenic

CF: Pathophysiology

1. CFTR gene mutation = Misfolded CFTR protein

• Required for ATP-gated Cl- channel

2. Low/No functioning ATP-gated Cl- channels in epithelial cell membranes

• Sweat Glands: Low Cl- reabsorption = Low Na+ and water reabsorption = High NaCl in sweat

• Endocrine Glands: Low Cl- and water secretion into lumen = High Na+ and water reabsorption = Hyperviscous mucus in lumen

  • Mucus blocks small passages → Organ damage

    • Lungs

    • Liver

    • Pancreas

    • Intestines

  • Increase infection risk

CF: Clinical Presentation

Salty sweat

GI:

• Meconium ileus**

  • Low mucous = No meconium (first stool) passing = Intestinal obstruction

• Rectal prolapse

• Malabsorption → Failure to thrive

  • Stunting and wasting

Resp:

• Recurrent infections

• COPD with bronchiectasis (bronchial dilation)

• Wheezing

• Dyspnea

CF: Investigations

NBS

Confirmatory tests

PFTs*

CXR and CT

CF: NBS

Positive → Confirmatory test

CF: Confirmatory Tests

Sweat Test

• Collect sweat + measure Cl-

• Positive: ≥ 60 mmol/L

• Borderline → Genetic test

Genetic Test

• Screen for carriers

• Determine targeted therapy

CF: PFT

Spirometry

Low FEV1:FVC

CF: CXR and CT

Air trapping and hyperinflation

Bronchiectasis

CF: Treatment

Antibiotics

• Prevent/suppress infections

High-energy diet

• Increase nutrition, NaCl, fat-soluble vitamins (ADEK)

• Pancreatic enzyme supplements

CFTR modulators

• Depend on mutation

CF Treatment: Preserve Lung Function

Pharmacological:

• Ibuprofen

• Bronchodilators (SABA, LABA)

• Mucolytics

Nonpharmacological:

• Conventional chest physiotherapy (CPT): Drain mucus

• Exercise

CF: Complications

Meconium ileus

Macronutrient malabsorption

Meconium Ileus

Clinical Presentation:

• Bilious vomiting

• Abdominal distension

Investigation: X-ray with contrast

• Dilated small bowel loops (inspissated meconium)

• Microcolon (small/narrow colon)

Treatment:

• Contrast enema (water-soluble)

  • Break down stool

• Surgery

Macronutrient Malabsorption

Pancreatic duct obstruction = Pancreatic enzyme deficiency (lipase, amylase, protease)