DIGESTION & ABSORPTION — CARBOHYDRATES

(Logic-Based, Zero-Omission Master Note)

PART 1️⃣ — BIG PICTURE: WHAT THE GIT DOES

Core purpose of the gastrointestinal system

• Acts as the portal of entry for:
• Nutritive substances
• Vitamins
• Minerals
• Fluids
• Large food molecules are not absorbable as they are → must be:
• Digested → broken into small units
• Absorbed → moved across intestinal epithelium into blood or lymph

Digestion vs Absorption (exam clarity)

• Digestion
• Chemical breakdown of food
• Converts macromolecules → absorbable units
• Occurs mainly in the small intestine (but starts earlier)
• Absorption
• Movement of digested products across intestinal mucosa
• Products enter:
• Blood (via portal circulation)
• Lymph (especially fats)

Enzymatic sources involved (orderly & sequential)

1. Salivary glands
• Begin carbohydrate digestion
• Minor fat digestion (species-dependent)
2. Stomach
• Protein digestion
• Some fat digestion
• Provides acidic environment (HCl)
3. Pancreas (exocrine)
• Digests:
• Carbohydrates
• Proteins
• Lipids
• DNA
• RNA
4. Small intestinal epithelial cells
• Final digestion occurs via:
• Brush border enzymes
• Cytoplasmic enzymes
5. Accessory secretions
• Hydrochloric acid (stomach) → optimal enzyme action
• Bile (liver) → aids lipid digestion

Transport principle across intestinal cells

• Substances usually:
1. Move from intestinal lumen → enterocyte
2. Then from enterocyte → interstitial fluid
• Important logic
• Transport across luminal membrane
• ≠ transport across basolateral membrane
• Different mechanisms are used on each side

PART 2️⃣ — CARBOHYDRATE DIGESTION: WHAT ENTERS THE GUT

Types of dietary carbohydrates

1. Polysaccharides
• Mainly starch
• Only polysaccharides humans can digest to a significant extent
2. Disaccharides
• Lactose (milk sugar)
• Sucrose (table sugar)
3. Monosaccharides
• Glucose
• Fructose

Structure of dietary starch (high-yield)

• Amylopectin
• ~75% of dietary starch
• Branched
• Contains:
• α-1,4 linkages
• α-1,6 branch points
• Amylose
• Straight chain
• Only α-1,4 linkages

PART 3️⃣ — STARCH DIGESTION STEP-BY-STEP

Step 1: Mouth (salivary phase)

• Enzyme: Salivary α-amylase
• Optimal pH: 6.7
• Begins starch digestion

🔹 Important nuance

• Enzyme remains partially active in the stomach
• Reason:
• Active site protected when substrate is present
• Despite acidic gastric juice

Step 2: Small intestine (major site)

• Enzymes acting
• Salivary α-amylase (continuing)
• Pancreatic α-amylase

What α-amylase DOES and DOES NOT do (exam trap zone)

α-amylase hydrolyzes

• Internal α-1,4 linkages

α-amylase SPARES

• α-1,6 linkages
• Terminal α-1,4 linkages

End products of α-amylase digestion

1. Maltose (disaccharide)
2. Maltotriose (trisaccharide)
3. α-limit dextrins
• Glucose polymers
• ~8 glucose units
• Contain α-1,6 linkages

PART 4️⃣ — BRUSH BORDER DIGESTION (FINAL STEP)

Location

• Brush border of small intestinal epithelial cells

Key oligosaccharidases & functions

1. Isomaltase

• Main enzyme for α-1,6 linkage hydrolysis
• Also breaks down:
• Maltose
• Maltotriose (with help of maltase & sucrase)

2. Sucrase

• Hydrolyzes:
• Sucrose → glucose + fructose

3. Lactase

• Hydrolyzes:
• Lactose → glucose + galactose

Structural biology detail (often ignored, but examinable)

• Sucrase + Isomaltase
• Synthesized as one glycoprotein chain
• Inserted into brush border membrane
• Later split by pancreatic proteases
• Final result:
• Separate functional sucrase
• Separate functional isomaltase

PART 5️⃣ — ENZYME DEFICIENCY → CLINICAL EFFECTS

What happens if brush border enzymes are deficient?

• Undigested oligosaccharides remain in lumen
• Consequences:
• Osmotic diarrhea
• Bloating
• Flatulence

Mechanisms explained logically

1. Osmotic diarrhea
• Undigested sugars = osmotically active
• Draw water into intestinal lumen
• ↑ volume of intestinal contents
2. Colon bacterial action
• Bacteria digest remaining oligosaccharides
• ↑ number of osmotic particles further
3. Gas production
• CO₂ and H₂ produced
• From disaccharide residues
• Causes bloating and flatulence

PART 6️⃣ — CARBOHYDRATE ABSORPTION: CORE PRINCIPLES

Where absorption occurs

• Small intestine
• Almost complete absorption before terminal ileum

Fate after absorption

• Sugars:
• Enter capillaries
• Drain into portal vein
• Reach the liver

PART 7️⃣ — GLUCOSE & GALACTOSE ABSORPTION (Na⁺-DEPENDENT)

Transporter involved

• SGLT (Sodium-dependent glucose transporter)
• Symport (Na⁺ + sugar together)

Key characteristics

• Requires Na⁺ in intestinal lumen
• High luminal Na⁺ → ↑ sugar uptake
• Low luminal Na⁺ → ↓ sugar uptake

Members of SGLT family

Structural features (exam detail)

• Cross membrane 12 times
• NH₂ and COOH terminals:
• On cytoplasmic side
• No homology with GLUT transporters

Mechanism logic (secondary active transport)

1. Intracellular Na⁺ is low
2. Na⁺ enters cell down its gradient
3. Glucose/galactose enter with Na⁺
4. Inside cell:
• Na⁺ pumped out
• Glucose exits via GLUT2
5. Energy source:
• Indirect
• From Na⁺ gradient maintained by Na⁺ pump

Clinical correlation

• Congenital SGLT defect →
• Glucose/galactose malabsorption
• Severe diarrhea
• Can be fatal unless sugars removed from diet

Therapeutic logic

• Glucose polymers used in diarrhea:
• Promote Na⁺ absorption
• Reduce fluid loss

PART 8️⃣ — FRUCTOSE ABSORPTION (Na⁺-INDEPENDENT)

Transport mechanism

• Facilitated diffusion

Transporters involved

• Luminal entry: GLUT5
• Basolateral exit: GLUT2

Additional detail

• Some fructose:
• Converted to glucose within mucosal cells

PART 9️⃣ — REGULATION & PHARMACOLOGY NOTES

Insulin effect

• Minimal effect on intestinal sugar absorption

Comparison with kidney

• Intestinal glucose absorption ≈ renal proximal tubule reabsorption
• Features shared:
• No phosphorylation required
• Normal in diabetes
• Inhibited by phlorizin

Capacity limit

• Max glucose absorption rate:
• ~120 g/hour

PART 🔟 — CLINICAL BOX: LACTOSE INTOLERANCE (FULLY CAPTURED)

Developmental pattern

• Lactase activity:
• High at birth
• Declines in childhood/adulthood in many populations

Population differences

Pathophysiology

• Low lactase →
• Lactose not digested
• Remains in lumen
• Bacterial fermentation in colon
• Produces gas + osmotic diarrhea

Symptoms

• Bloating
• Pain
• Gas
• Diarrhea

Management

1. Avoid dairy products
2. Lactase supplements (effective but costly)
3. Yogurt better tolerated:
• Contains bacterial lactase

PART 1️⃣1️⃣ — TABLE 26-1: ABSORPTION DISTRIBUTION (INTERPRETED)

Key patterns (logic summary)

• Jejunum:
• Major site for:
• Sugars
• Amino acids
• Vitamins
• Minerals (Ca²⁺, Fe²⁺)
• Ileum:
• Specialized absorption:
• Bile acids
• Vitamin B12
• Antibodies (newborns)
• Colon:
• Strong Na⁺ absorption
• K⁺ secretion when luminal K⁺ is low

Duodenum special note

• Similar to jejunum except:
• Secretes HCO₃⁻
• Little net NaCl absorption

PROTEINS & NUCLEIC ACIDS — DIGESTION + ABSORPTION

(Logic-Based, Zero-Omission Master Note)

PART 1️⃣ — PROTEIN DIGESTION: STARTS IN STOMACH

1.1 Where it begins + main enzyme group

• Protein digestion begins in the stomach
• Pepsins cleave some peptide bonds (not all digestion—just the start)

1.2 Proenzyme logic (why pepsin is “inactive first”)

• Like many protein-digesting enzymes, pepsins are released as inactive precursors (proenzymes)
• Pepsin precursors are called pepsinogens
• Activation trigger: gastric acid

1.3 Types of pepsinogen in humans (exam detail)

• Human gastric mucosa contains multiple related pepsinogens → grouped into:
• Pepsinogen I
• Pepsinogen II
• Pepsinogen I:
• Found only in acid-secreting regions
• Pepsinogen II:
• Also found in the pyloric region (so not restricted to acid-secreting areas)
• Clinical correlation:
• Maximal acid secretion correlates with pepsinogen I levels

PART 2️⃣ — WHAT PEPSIN CUTS + WHEN IT STOPS

2.1 What bonds pepsin prefers

• Pepsins hydrolyze bonds between an aromatic amino acid and a second amino acid
• Aromatic examples explicitly given:
• Phenylalanine
• Tyrosine
• Result: peptic digestion produces polypeptides of widely varying sizes

2.2 Pepsin pH optimum + why action ends

• Pepsins have a very acidic pH optimum: 1.6–3.2
• Pepsin action is terminated when gastric contents mix with alkaline pancreatic juice in:
• Duodenum
• Jejunum

2.3 pH values along early intestine (numbers you must keep)

• Duodenal bulb pH: 3.0–4.0
• Then pH rises quickly
• Rest of duodenum pH: about 6.5

PART 3️⃣ — SMALL INTESTINE: PANCREATIC + MUCOSAL PROTEASES FINISH THE JOB

3.1 What happens to stomach-made polypeptides

• Polypeptides formed in the stomach are further digested in the small intestine by:
• Powerful pancreatic proteolytic enzymes
• Intestinal mucosal enzymes

3.2 Endopeptidases (cut inside peptide chain)

• Trypsin
• Chymotrypsins
• Elastase
• These act on interior peptide bonds → therefore called endopeptidases

PART 4️⃣ — ACTIVATION CASCADE: WHY THEY DON’T DIGEST THE PANCREAS

4.1 Core rule

• Active endopeptidases are formed from inactive precursors only at the site of action
• Triggered by a brush-border enzyme:
• Enterokinase (brush border hydrolase)

4.2 Pancreatic enzymes are secreted inactive (safety logic)

• Protein-splitting enzymes in pancreatic juice are secreted as inactive proenzymes
• Key conversion:
• Trypsinogen → Trypsin
• Activated by enterokinase when pancreatic juice enters the duodenum

4.3 Enterokinase special composition detail (why it survives)

• Enterokinase contains 41% polysaccharide
• This high polysaccharide content apparently protects it from being digested before it acts

4.4 Trypsin = master activator (cascade logic)

• Trypsin converts:
• Chymotrypsinogens → Chymotrypsins
• Other proenzymes → active enzymes
• Trypsin can also activate trypsinogen itself
• So once a little trypsin forms → auto-catalytic chain reaction amplifies digestion

4.5 Clinical consequence

• Congenital enterokinase deficiency
• Leads to protein malnutrition

PART 5️⃣ — EXOPEPTIDASES + BRUSH BORDER ENZYMES: FINAL CLEAVAGE TO AMINO ACIDS

5.1 Carboxypeptidases (pancreas) = exopeptidases

• Pancreatic carboxypeptidases are exopeptidases
• They hydrolyze amino acids from the carboxyl (C-terminal) end of polypeptides

5.2 Where amino acids are liberated (multiple locations)

• Some free amino acids are released in the intestinal lumen
• Others are liberated right at the cell surface (brush border) by brush border enzymes:
• Aminopeptidases
• Carboxypeptidases
• Endopeptidases
• Dipeptidases

5.3 Peptide absorption + intracellular finishing

• Some dipeptides and tripeptides are:
• Actively transported into enterocytes
• Then hydrolyzed by intracellular peptidases
• Amino acids then enter the bloodstream

✅ Therefore: final digestion to amino acids occurs in 3 places

1. Intestinal lumen
2. Brush border
3. Cytoplasm of mucosal cells

PART 6️⃣ — ABSORPTION OF AMINO ACIDS + PEPTIDES

6.1 Amino acid transport systems (numbers matter)

• At least 7 different transport systems move amino acids into enterocytes
• Of these:
• 5 require Na⁺ and cotransport amino acids + Na⁺ (analogous to Na⁺-glucose cotransport)
• 2 of those 5 also require Cl⁻
• 2 systems are Na⁺-independent

6.2 Dipeptide/tripeptide transporter

• Dipeptides + tripeptides enter enterocytes via:
• PepT1 (peptide transporter 1)
• It requires H⁺ (not Na⁺)

6.3 Larger peptides

• There is very little absorption of larger peptides

6.4 Basolateral exit into blood

• Inside enterocytes, amino acids come from:
• Intracellular peptide hydrolysis
• Plus amino acids absorbed from lumen/brush border
• These amino acids exit enterocytes at basolateral membrane via at least 5 transport systems
• Then enter hepatic portal blood

PART 7️⃣ — WHERE ABSORPTION IS MAXIMUM + PROTEIN SOURCES IN THE GUT

7.1 Location of rapid absorption

• Amino acid absorption is rapid in duodenum and jejunum
• Only a little absorption happens in the ileum in health because:
• Most amino acids already absorbed by then

7.2 Where “digested protein” in the intestine comes from (percentages)

Approximate contribution to digested protein pool:

• 50% from ingested food
• 25% from proteins in digestive juices
• 25% from desquamated mucosal cells

7.3 How much escapes absorption

• Only 2–5% of protein in the small intestine:
• escapes digestion and absorption
• Some of that is eventually digested by colonic bacteria

7.4 What protein in stool actually is (exam trap)

• Almost all protein in stools is NOT dietary
• Comes mainly from:
• Bacteria
• Cellular debris

PART 8️⃣ — REGULATION + GENETIC TRANSPORT DEFECTS (CLINICAL)

8.1 Evidence for homeostatic regulation of peptidases

• Evidence suggests brush border + cytoplasmic peptidase activities:
• Increase after resection of part of the ileum
• Are independently altered in starvation
• Meaning: these enzymes show homeostatic regulation

8.2 Hartnup disease (neutral amino acids)

• Congenital defect of transport mechanism for neutral amino acids
• Affects:
• Intestine
• Renal tubules
• Causes Hartnup disease

8.3 Cystinuria (basic amino acids)

• Congenital defect in transport of basic amino acids
• Causes cystinuria

8.4 Why nutrition often stays okay despite these defects

• Most patients don’t get nutritional deficiencies because:
• Peptide transport compensates (PepT-type transport saves the day)

PART 9️⃣ — INTACT PROTEIN ABSORPTION: INFANTS, ADULTS, ALLERGY

9.1 Infants absorb moderate undigested proteins

• In infants, moderate amounts of undigested proteins are absorbed

Colostrum antibodies (what + where + how)

• Antibodies in maternal colostrum are largely:
• Secretory IgA
• IgA production in breast:
• Increased in late pregnancy
• They cross mammary epithelium by:
• Transcytosis
• In infant intestine:
• Enter circulation from intestine → provides passive immunity
• Mechanism of absorption:
• Endocytosis → then exocytosis

9.2 After weaning + adult state

• Absorption of intact proteins:
• Declines sharply after weaning
• Adults still absorb:
• small quantities

9.3 Allergy mechanism link (why intact protein absorption matters)

• Foreign proteins entering circulation:
• provoke antibody formation
• On later exposure:
• antigen–antibody reactions may cause allergic symptoms
• This helps explain food allergies after certain meals

Incidence + common offenders

• Food allergy incidence in children: up to 8%
• Common offenders listed:
• Crustaceans
• Mollusks
• Fish
• Also frequent:
• Legumes
• Cow’s milk
• Egg white
• Most individuals don’t develop food allergy
• There is evidence for a genetic susceptibility component

PART 🔟 — M CELLS + PEYER PATCHES: MUCOSAL IMMUNITY PATHWAY

10.1 Where antigen absorption happens

• Protein antigens (especially bacterial/viral) are absorbed via:
• Microfold (M) cells
• These are specialized intestinal epithelial cells that overlie:
• Lymphoid aggregates (Peyer patches)

10.2 What happens to the antigen

• M cells pass antigens to lymphoid cells
• Lymphocytes become activated

10.3 What activated lymphoblasts do

• Activated lymphoblasts:
• Enter circulation
• Later return (“home back”) to:
• Intestinal mucosa
• Other epithelia
• There they secrete IgA on later exposure to same antigen

10.4 Why this matters

• This secretory immunity is a major defense mechanism

PART 1️⃣1️⃣ — NUCLEIC ACIDS: DIGESTION + ABSORPTION

11.1 Digestion steps (sequence must be kept)

1. Pancreatic nucleases
• Split nucleic acids → nucleotides
2. Enzymes on luminal surface of mucosal cells
• Split nucleotides → nucleosides + phosphoric acid
3. Nucleosides then split into:
• Sugars
• Purine bases
• Pyrimidine bases

11.2 Absorption mechanism

• The bases are absorbed by active transport

11.3 Transporter families (modern detail kept)

• Two transporter families have been identified and are expressed on the apical membrane of enterocytes:
• Equilibrative nucleoside transporters (passive)
• Concentrative nucleoside transporters (secondary active)

LIPIDS — DIGESTION, ABSORPTION & COLONIC SCFAs

(Logic-Based, Zero-Omission Master Note)

PART 1️⃣ — FAT DIGESTION: WHERE IT STARTS (MINOR CONTRIBUTORS)

1.1 Non-pancreatic lipases (early phase)

• Lingual lipase
• Secreted by Ebner glands on the dorsal surface of the tongue
• Present in some species
• Gastric lipase
• Secreted by the stomach

1.2 Quantitative importance (key logic)

• These lipases are of little quantitative importance for fat digestion under normal conditions
• They become relevant:
• In pancreatic insufficiency
• Additional signaling role:
• They may generate free fatty acids
• These FFAs can signal to distal GI tract
• Example: stimulate CCK release

PART 2️⃣ — MAJOR FAT DIGESTION: DUODENUM + PANCREATIC LIPASE

2.1 Main enzyme

• Pancreatic lipase
• One of the most important enzymes in fat digestion
• Acts primarily in the duodenum

2.2 Bond specificity (exam-critical)

• Hydrolyzes:
• 1-bond of triglycerides
• 3-bond of triglycerides
• With relative ease
• Acts on:
• 2-bond → very slowly

2.3 End products of pancreatic lipase

• Free fatty acids
• 2-monoglycerides (2-monoacylglycerols)

2.4 Requirement for emulsification

• Lipase acts only on emulsified fats

PART 3️⃣ — LIPASE STRUCTURE, COLIPASE & ACTIVATION LOGIC

3.1 “Lid” mechanism of pancreatic lipase

• Pancreatic lipase has:
• An amphipathic helix
• Covers the active site like a lid
• Enzyme becomes active when:
• This lid is bent back

3.2 Colipase — what it is and why it matters

• Colipase
• Protein
• Molecular weight ≈ 11,000
• Secreted in pancreatic juice

3.3 How colipase works

• Binds to the –COOH-terminal domain of pancreatic lipase
• This:
• Facilitates opening of the lipase “lid”
• Colipase is essential because:
• Allows lipase to remain attached to lipid droplets
• Even in the presence of bile acids

3.4 Activation of colipase

• Secreted as an inactive proform
• Activated in intestinal lumen by:
• Trypsin

PART 4️⃣ — OTHER PANCREATIC LIPOLYTIC ENZYMES

4.1 Cholesterol esterase (bile-acid–activated lipase)

• Another pancreatic lipase
• Activated by bile acids
• Molecular weight ≈ 100,000 Da
• Constitutes about 4% of total pancreatic juice protein

4.2 Comparison with pancreatic lipase

• In adults:
• Pancreatic lipase is 10–60× more active
• However, cholesterol esterase uniquely hydrolyzes:
• Cholesterol esters
• Esters of fat-soluble vitamins
• Phospholipids
• Triglycerides

4.3 Special note

• A very similar enzyme is present in human milk

PART 5️⃣ — BILE, EMULSIFICATION & MICELLES (CORE CONCEPT)

5.1 Problem: fat insolubility

• Fats are relatively insoluble
• This limits their ability to:
• Cross the unstirred water layer
• Reach the mucosal surface

5.2 Solution: emulsification

• In small intestine, fats are finely emulsified by:
• Bile acids
• Phosphatidylcholine
• Monoglycerides
• These act as detergents

PART 6️⃣ — MICELLES: FORMATION, STRUCTURE & FUNCTION

6.1 When micelles form

• When bile acid concentration is high
• Especially after gallbladder contraction
• Lipids + bile acids interact spontaneously

6.2 Micelle structure

• Cylindrical aggregates
• Hydrophobic core contains:
• Fatty acids
• Monoglycerides
• Cholesterol
• Amphipathic molecules:
• Phospholipids & monoglycerides
• Hydrophilic heads → outside
• Hydrophobic tails → inside

6.3 Functional role of micelles

• Further solubilize lipids
• Provide transport mechanism through:
• Unstirred layer
• Micelles move:
• Down their concentration gradient
• To the brush border

6.4 Final delivery to enterocyte

• Lipids diffuse out of micelles
• Maintains:
• Saturated aqueous lipid solution
• In contact with brush border
• Micelles themselves are not absorbed

PART 7️⃣ — STEATORRHEA: PATHOPHYSIOLOGY (EXAM FAVORITE)

7.1 What steatorrhea looks like

• Fatty
• Bulky
• Clay-colored stools

7.2 Causes related to pancreas

• Seen in:
• Pancreatectomized animals
• Diseases destroying exocrine pancreas
• Primary mechanism:
• Lipase deficiency

7.3 Role of acid & bicarbonate

• Lipase is acid-inhibited
• Pancreatic disease → ↓ alkaline secretion
• → Intestinal pH falls
• → Lipase activity further reduced
• Hypersecretion of gastric acid can also cause steatorrhea

7.4 Bile acid–related causes

• Defective bile acid reabsorption in distal ileum
• If bile is excluded from intestine:
• Up to 50% of ingested fat appears in feces
• Severe malabsorption of fat-soluble vitamins

7.5 Enterohepatic circulation interruption

• Terminal ileal resection or disease:
• Interrupts bile acid recycling
• Liver cannot increase bile acid synthesis enough
• Result:
• Increased fat loss in stool

PART 8️⃣ — FAT ABSORPTION: ENTEROCYTE HANDLING

8.1 Entry into enterocytes

• Traditionally thought:
• Passive diffusion
• Now evidence suggests:
• Carrier-mediated transport also involved

8.2 Intracellular trapping mechanism

• Inside enterocytes:
• Lipids are rapidly esterified
• This:
• Maintains favorable concentration gradient
• Promotes continued uptake

8.3 Export back into lumen (availability control)

• Certain lipids are exported back into lumen
• Limits oral availability
• Applies to:
• Plant sterols
• Cholesterol

PART 9️⃣ — SHORT- VS LONG-CHAIN FATTY ACIDS (CRITICAL SPLIT)

9.1 Short-chain / medium-chain fatty acids

• <10–12 carbon atoms
• Water-soluble enough to:
• Pass through enterocyte unmodified
• Transport:
• Actively transported into portal blood
• Circulation:
• As free (unesterified) fatty acids

9.2 Long-chain fatty acids

• >10–12 carbon atoms
• Too insoluble for portal transport
• Inside enterocytes:
• Re-esterified to triglycerides
• Some absorbed cholesterol:
• Esterified to cholesterol esters

PART 🔟 — CHYLOMICRON FORMATION & EXPORT

10.1 What goes into chylomicrons

• Triglycerides
• Cholesterol esters
• Coated with:
• Protein
• Cholesterol
• Phospholipids

10.2 Why lymphatics are used

• Chylomicrons are too large
• Cannot pass through capillary endothelial junctions
• Therefore enter:
• Lymphatics

PART 1️⃣1️⃣ — INTRACELLULAR LIPID PROCESSING (ORGANELLE-WISE)

11.1 Triglyceride synthesis pathways

• Majority formed by:
• Acylation of absorbed 2-monoglycerides
• Occurs mainly in smooth ER
• Some triglycerides formed from:
• Glycerophosphate
• Derived from glucose catabolism

11.2 Phospholipids & lipoproteins

• Glycerophosphate also forms:
• Glycerophospholipids
• Acylation + lipoprotein assembly:
• Occur in rough ER

11.3 Golgi processing

• Carbohydrate moieties added to proteins
• Occurs in Golgi apparatus

11.4 Final export

• Completed chylomicrons:
• Extruded by exocytosis
• From basolateral surface

PART 1️⃣2️⃣ — SITE & EFFICIENCY OF FAT ABSORPTION

12.1 Regional absorption

• Long-chain fatty acid absorption:
• Greatest in upper small intestine
• Still significant in ileum

12.2 Efficiency

• With moderate fat intake:
• ≥95% of ingested fat absorbed

12.3 Neonatal limitation

• Fat absorption mechanisms immature at birth
• Infants fail to absorb:
• 10–15% of ingested fat
• Therefore:
• More susceptible to diseases reducing fat absorption

PART 1️⃣3️⃣ — SHORT-CHAIN FATTY ACIDS (SCFAs) IN THE COLON

13.1 What SCFAs are

• 2–5 carbon weak acids
• Average luminal concentration:
• ~80 mmol/L

13.2 Composition

• Acetate → ~60%
• Propionate → ~25%
• Butyrate → ~15%

13.3 Source

• Produced by colonic bacteria
• Act on:
• Complex carbohydrates
• Resistant starches
• Dietary fiber
• Fiber = material escaping digestion in upper GI tract

PART 1️⃣4️⃣ — FUNCTIONS & ABSORPTION OF SCFAs

14.1 Metabolic role

• Absorbed SCFAs:
• Are metabolized
• Contribute significantly to total caloric intake

14.2 Local intestinal effects

• Trophic effect on colonic epithelial cells
• Anti-inflammatory action

14.3 Acid–base role

• Absorbed partly in exchange for H⁺
• Helps maintain acid–base balance

14.4 Transport mechanisms

• Absorbed by specific SCFA transporters
• Present in colonic epithelial cells

14.5 Sodium absorption link

• SCFAs promote Na⁺ absorption
• Exact mechanism of Na⁺–SCFA coupling:
• Not fully settled

ABSORPTION OF VITAMINS & MINERALS

Logic-based integrated note (ZERO omission)

PART 1️⃣ — VITAMINS: GENERAL PRINCIPLES

What are vitamins? (definition logic)

• Vitamins are small organic molecules
• They are essential for biochemical reactions
• They cannot be synthesized adequately in the body
• Therefore, they must be obtained from the diet

📌 This definition explains why absorption mechanisms are critical.

PART 2️⃣ — FAT-SOLUBLE VITAMINS (A, D, E, K)

Ingestion form

• Vitamins A, D, E, K are ingested as esters

Digestion requirement

• These esters must be digested by cholesterol esterase
• Without this enzymatic step → absorption cannot occur

Solubility problem

• Fat-soluble vitamins are highly insoluble in the aqueous intestinal lumen
• Therefore, free diffusion is impossible

Micelle dependence (KEY LOGIC)

• Absorption is entirely dependent on incorporation into bile salt micelles
• No micelles → no absorption

Causes of malabsorption (EXAM TRAPS)

Absorption is impaired when:

1. Pancreatic enzyme deficiency
• ↓ cholesterol esterase
• ↓ fat digestion
2. Bile duct obstruction
• Bile excluded from intestine
• No micelle formation

📌 Any condition causing fat malabsorption → fat-soluble vitamin deficiency

PART 3️⃣ — WATER-SOLUBLE VITAMINS: SITE & MECHANISM

Site of absorption

• Most vitamins → absorbed in the upper small intestine
• Exception: Vitamin B12 → absorbed in the ileum

PART 4️⃣ — VITAMIN B12 (COBALAMIN)

Binding requirement

• Vitamin B12 binds to intrinsic factor (IF)
• Intrinsic factor is:
• A protein
• Secreted by parietal cells of the stomach

Absorption mechanism

• B12–IF complex binds to receptors
• Absorbed across the ileal mucosa

Sodium dependence

• Vitamin B12 absorption is Na⁺-independent

📌 Loss of parietal cells → IF deficiency → B12 malabsorption

PART 5️⃣ — FOLATE VS OTHER WATER-SOLUBLE VITAMINS

Sodium dependence comparison

• Na⁺-independent absorption
• Vitamin B12
• Folate
• Na⁺-dependent absorption
• Remaining 7 water-soluble vitamins

Na⁺-cotransporter-dependent vitamins (LIST — ZERO omission)

All absorbed via Na⁺ cotransporters:

1. Thiamin (B1)
2. Riboflavin (B2)
3. Niacin (B3)
4. Pyridoxine (B6)
5. Pantothenate (B5)
6. Biotin
7. Ascorbic acid (Vitamin C)

📌 Loss of Na⁺ gradient → impaired absorption of these vitamins

PART 6️⃣ — CALCIUM (Ca²⁺) ABSORPTION

Fraction absorbed

• 30–80% of ingested calcium is absorbed
• Wide range reflects physiological regulation

Role of Vitamin D

• Absorption regulated by 1,25-dihydroxycholecalciferol
• This adjusts Ca²⁺ absorption according to body needs:

Dietary modifiers

Facilitators

• Protein → enhances Ca²⁺ absorption
• Protein also facilitates magnesium absorption

Inhibitors (INSOLUBLE SALT LOGIC)

• Phosphates
• Oxalates

These form insoluble calcium salts in the intestine → ↓ absorption

📌 High oxalate diet = low calcium bioavailability

PART 7️⃣ — IRON: OVERVIEW & BALANCE LOGIC

Iron loss (unregulated)

• Iron losses occur passively
• Regulation occurs at the level of intestinal absorption

Daily losses

• Men: ~0.6 mg/day (mainly fecal)
• Premenopausal women:
• ~double this amount
• Due to menstrual blood loss

PART 8️⃣ — DIETARY IRON INTAKE VS ABSORPTION

Intake

• Average intake: ~20 mg/day (US & Europe)

Absorption efficiency

• Only 3–6% of ingested iron is absorbed
• Absorbed amount ≈ daily losses

📌 Hence iron deficiency is common when absorption is impaired

PART 9️⃣ — DIETARY FACTORS AFFECTING IRON AVAILABILITY

Inhibitors (INSOLUBLE COMPLEXES)

• Phytic acid (cereals)
• Phosphates
• Oxalates

→ All form insoluble iron compounds → ↓ absorption

PART 🔟 — IRON OXIDATION STATE (CRITICAL EXAM LOGIC)

Dietary form

• Most dietary iron is ferric (Fe³⁺)

Absorbable form

• Only ferrous (Fe²⁺) iron is absorbed

Brush border reduction

• Fe³⁺ reductase present at enterocyte brush border
• Associated with iron transporter

PART 1️⃣1️⃣ — ROLE OF GASTRIC SECRETIONS

Functions

• Dissolve dietary iron
• Promote formation of soluble complexes with:
• Ascorbic acid
• Other reducing substances

Clinical correlation (VERY HIGH YIELD)

• Partial gastrectomy →
• ↓ gastric acid
• ↓ Fe³⁺ reduction
• → iron deficiency anemia

PART 1️⃣2️⃣ — SITE & TRANSPORT OF IRON ABSORPTION

Site

• Almost all iron absorption occurs in the duodenum

Apical transport

• Fe²⁺ enters enterocyte via:
• Divalent Metal Transporter-1 (DMT1)

PART 1️⃣3️⃣ — INTRACELLULAR IRON HANDLING

Two possible fates inside enterocyte

1. Storage
• Stored as ferritin
2. Export
• Transported across basolateral membrane

Basolateral export

• Exported via ferroportin-1

Role of hephaestin

• Hephaestin (Hp):
• Not a transporter
• Facilitates basolateral iron transport

PART 1️⃣4️⃣ — PLASMA IRON TRANSPORT

Oxidation & binding

• Fe²⁺ → converted to Fe³⁺
• Bound to transferrin

Transferrin facts

• Has two iron-binding sites
• Normally ~35% saturated

Normal plasma iron levels

• Men: ~130 μg/dL (23 μmol/L)
• Women: ~110 μg/dL (19 μmol/L)

PART 1️⃣5️⃣ — HEME IRON ABSORPTION

Apical uptake

• Heme binds to a specific apical transport protein
• Transported intact into enterocyte

Cytoplasmic processing

• Heme oxygenase-2 (HO-2):
• Removes Fe²⁺ from porphyrin ring
• Adds iron to intracellular Fe²⁺ pool

PART 1️⃣6️⃣ — IRON DISTRIBUTION IN THE BODY

Percentage distribution

• 70% → hemoglobin
• 3% → myoglobin
• Remainder → ferritin stores

Ferritin structure

• Composed of apoferritin
• Apoferritin:
• Globular protein
• 24 subunits

Microscopy & pathology

• Ferritin:
• Electron-dense
• Used as tracer in phagocytosis studies
• Hemosiderin:
• Aggregated ferritin in lysosomes
• Can contain up to 50% iron

PART 1️⃣7️⃣ — REGULATION OF INTESTINAL IRON ABSORPTION

Iron absorption regulated by THREE factors:

1. Recent dietary iron intake
2. Body iron stores
3. Erythropoietic activity of bone marrow

📌 Proper regulation is essential for health

🔴 PART 1: DISORDERS OF IRON UPTAKE (CLINICAL BOX 26–2)

1️⃣ Iron imbalance — core logic

• Iron deficiency → ↓ hemoglobin synthesis → iron-deficiency anemia
• Iron excess → iron stored as hemosiderin
• Accumulation of hemosiderin in tissues = hemosiderosis
• Excessive deposition → tissue damage

👉 Key contrast

• Deficiency → functional failure (anemia)
• Excess → toxic tissue injury

2️⃣ Hemochromatosis — definition & consequences

Hemochromatosis = pathological iron overload causing organ damage

Major affected organs & manifestations:

• Skin → pigmentation
• Pancreas → β-cell damage → diabetes

→ classic “bronze diabetes”

• Liver:
• Cirrhosis
• ↑ risk of hepatocellular carcinoma
• Gonads → gonadal atrophy

👉 This is not just iron storage — it is organ-destructive iron toxicity

3️⃣ Types of hemochromatosis

A️⃣ Hereditary hemochromatosis

• Most common cause: mutation of HFE gene
• Epidemiology:
• Common in white population
• Genetics:
• Located on short arm of chromosome 6
• Closely linked to HLA-A locus
• Pathophysiology:
• Normal HFE inhibits duodenal iron transporters
• Mutated HFE → loss of inhibition
• Result → excess iron absorption from intestine
• Critical detail:
• Disease occurs especially in homozygous individuals

⚠️ Important exam nuance:

Mechanism is not fully understood, but increased intestinal absorption is the key abnormality.

B️⃣ Acquired hemochromatosis

Occurs when iron regulation is overwhelmed, not genetically broken

Common causes:

• Chronic hemolysis → continuous iron release
• Chronic liver disease
• Repeated blood transfusions
• Especially in intractable anemias

👉 Exam logic:

Hereditary = ↑ absorption

Acquired = ↑ iron load beyond regulatory capacity

4️⃣ Therapeutic highlight (iron overload)

• Early diagnosis is critical
• If detected before tissue saturation:
• Repeated phlebotomy (blood withdrawal):
• Removes iron directly
• Significantly prolongs life expectancy

🔴 PART 2: CONTROL OF FOOD INTAKE — OVERALL FRAMEWORK

1️⃣ Big picture control system

Food intake is regulated by:

• Peripheral signals
• Central nervous system (hypothalamus)
• Higher brain functions

Modulating factors:

• Food preferences
• Emotions
• Environment
• Lifestyle
• Circadian rhythms

👉 Feeding is not reflex-only — cognition matters

2️⃣ Gut hormones as feeding regulators

Many hormones released during meals:

• Aid digestion
• Also regulate appetite

These signals act as:

• Anorexins → suppress intake
• Orexins → stimulate intake

3️⃣ Cholecystokinin (CCK) — satiety hormone

Sources:

• I cells of intestine
• Central neurons

Actions:

• Inhibits further food intake
• Acts as a satiety factor (anorexin)

Clinical relevance:

• Target for anti-obesity drug development
• Interest increased due to obesity epidemic

🔴 PART 3: LEPTIN vs GHRELIN — RECIPROCAL CONTROL

1️⃣ Leptin — long-term energy balance

Source:

• Adipose tissue

Signal conveyed:

• Status of fat stores

Effects:

• ↑ leptin secretion as adipocytes enlarge
• ↓ food intake via hypothalamic action
• ↑ metabolic rate

Hypothalamic actions:

• ↑ anorexigenic factors:
• POMC
• CART
• Neurotensin
• CRH

Pathology:

• Leptin resistance:
• Adequate or high fat stores
• Appetite suppression fails
• → obesity

2️⃣ Ghrelin — meal initiator

Source:

• Mainly stomach
• Also pancreas & adrenal glands

Secretion pattern:

• ↑ before meals
• ↓ after meals

Actions:

• Stimulates appetite (orexin)
• Initiates meals (short-term signal)

Central effects:

• ↑ orexins:
• Neuropeptide Y
• Cannabinoids
• ↓ leptin-mediated anorexigenic signaling

3️⃣ Leptin–ghrelin reciprocity

• Leptin normally suppresses ghrelin
• Ghrelin antagonizes leptin effects
• In obesity:
• Leptin resistance
• Loss of leptin-mediated ghrelin suppression

Clinical insight:

• ↓ ghrelin after gastric bypass
• Explains early metabolic benefits before weight loss

🔴 PART 4: OBESITY (CLINICAL BOX 26–3)

1️⃣ Definition & measurement

BMI = weight (kg) / height² (m²)

• Normal: <25
• Overweight: 25–30
• Obese: >30

2️⃣ Epidemiology

• USA:
• 34% overweight
• 34% obese
• Global:
• Overweight ≈ undernourished population worldwide

3️⃣ Complications of obesity

• Accelerated atherosclerosis
• Gallbladder disease
• Type 2 diabetes:
• ↑ insulin resistance with ↑ weight
• Weight loss → glucose tolerance improves
• ↑ mortality from multiple cancers

4️⃣ Etiology — why obesity happens

• Genetic component:
• Twin studies support heredity
• Evolutionary logic:
• Fat storage once adaptive
• Now maladaptive in food-rich environments
• Fundamental cause:
• Energy intake > energy expenditure
• Individual variation:
• Differences in NEAT
• Ageing:
• Gradual weight gain through adult life
• Hormonal:
• ↓ leptin sensitivity with time

5️⃣ Treatment principles

• Long-term success requires:
• ↓ food intake
• ↑ energy expenditure
• Exercise alone:
• Often insufficient (induces compensatory eating)
• Severe obesity:
• Bariatric surgery
• Restricts intake
• Alters gut hormones
• Pharmacology:
• Targeting orexins/anorexins under investigation

🔴 PART 5: NUTRITIONAL PRINCIPLES & ENERGY METABOLISM

1️⃣ Catabolism vs anabolism

• Catabolism:
• Stepwise oxidation
• Releases usable energy
• Anabolism:
• Energy-consuming synthesis
• Storage as:
• Glycogen
• Fat
• Protein

2️⃣ Energy output equation

Energy output = Work + Storage + Heat

• Resting, fasting adult:
• Nearly all energy → heat

3️⃣ Metabolic rate

• Energy liberated per unit time
• Muscle efficiency:
• Isotonic contraction ≈ 50%
• Isometric contraction → heat only

🔴 PART 6: CALORIES

• 1 calorie (cal):
• Raises 1 g water by 1°C
• 1 Calorie (kcal) = 1000 cal

Energy content:

• Carbohydrate: 4.1 kcal/g
• Fat: 9.3 kcal/g
• Protein:
• Bomb calorimeter: 5.3 kcal/g
• In body: 4.1 kcal/g (incomplete oxidation)

🔴 PART 7: RESPIRATORY QUOTIENT (RQ)

Definition:

RQ = CO₂ produced / O₂ consumed (steady state)

Values:

• Carbohydrate: 1.00
• Fat: 0.70
• Protein: 0.82

Clinical variations:

• Hyperventilation → R ↑
• Strenuous exercise → R up to 2.0
• Post-exercise → R ↓ (<0.5)
• Metabolic acidosis → R ↑
• Metabolic alkalosis → R ↓

Organ-specific:

• Brain RQ ≈ 0.97–0.99
• Stomach during acid secretion → negative R

🔴 PART 8: FACTORS AFFECTING METABOLIC RATE

Major influences:

• Muscular activity
• Food intake (SDA)
• Environmental temperature (U-shaped curve)
• Age, sex, body size
• Growth, pregnancy, lactation
• Emotional state
• Body temperature
• Thyroid hormones
• Catecholamines

🔴 PART 9: BASAL METABOLIC RATE (BMR)

• Measured:
• At rest
• Thermoneutral environment
• 12–14 h fasting
• Falls:
• Sleep (~10%)
• Starvation (up to 40%)
• Average adult male:
• ~2000 kcal/day
• Relation to weight:
• BMR = 3.52 × W⁰·⁷⁵

🔴 PART 10: ENERGY BALANCE

• Negative balance → weight loss
• Positive balance → weight gain
• First law of thermodynamics applies fully

Typical needs:

• Basal: ~2000 kcal/day
• Sedentary activity: +500 kcal
• Heavy labor: +3000 kcal

🥗 NUTRITION — LOGIC-BASED MASTER NOTE (ZERO OMISSION)

PART 1️⃣ — BIG PICTURE: WHAT IS NUTRITION?

Core Aim

• Nutrition science determines:
• Which foods
• In what amounts

→ best promote health and well-being

Scope (Important)

Nutrition is NOT just deficiency.

It includes:

• Undernutrition
• Overnutrition
• Taste preferences
• Food availability
• Economic & social factors

Key Principle

Even with all this variation, some substances are essential in every human diet.

PART 2️⃣ — ESSENTIAL DIETARY COMPONENTS

What an optimal diet MUST contain

In addition to adequate water, an optimal diet includes:

• Calories
• Protein
• Fat
• Minerals
• Vitamins

👉 Water is essential, but detailed elsewhere.

PART 3️⃣ — CALORIC INTAKE: BALANCE LOGIC

Energy Balance Rule

• Calories eaten ≈ calories expended

→ body weight remains stable

Daily Energy Needs

• ~2000 kcal/day → basal metabolic needs
• + 500–2500 kcal/day (or more) → daily physical activity
• Total depends on activity level

PART 4️⃣ — CALORIC DISTRIBUTION (MACRONUTRIENTS)

What decides distribution?

Calories are split between:

• Carbohydrate
• Protein
• Fat

Based on:

• Physiologic needs
• Taste
• Economics

PART 5️⃣ — PROTEIN REQUIREMENTS (CRITICAL)

Amount

• 1 g/kg body weight/day
• Purpose:
• Supply 8 essential amino acids
• Plus non-essential amino acids

Protein Quality Matters

Proteins are classified by amino-acid composition:

🥩 Grade I Proteins

• Animal proteins:
• Meat
• Fish
• Dairy
• Eggs
• Contain amino acids in ideal proportions
• Efficient for protein synthesis

🌾 Grade II Proteins

• Most plant proteins
• Problems:
• Imbalanced amino acid proportions
• May lack one or more essential amino acids

Important Logic

• Protein needs can be met with Grade II proteins
• BUT:
• Intake must be much larger
• Due to amino acid wastage

PART 6️⃣ — FAT: ENERGY, COST & HEALTH

Energy Density

• Fat provides 9.3 kcal/g

→ most compact energy source

Cost & Society

• Often most expensive macronutrient
• Globally:
• Higher fat intake ↔ higher standard of living

Western Diet Pattern

• Historically ~100 g/day or more
• Trends changing due to:
• Obesity prevention
• Atherosclerosis prevention

Fat Quality Matters

• High unsaturated : saturated fat ratio

→ beneficial for atherosclerosis prevention

Very Important Observation

• Some populations (e.g., Central & South American Indian communities):
• Corn-based (high carbohydrate)
• Very low fat intake
• No ill effects over years

Key Conclusion

• Low fat intake is NOT harmful

IF:

• Essential fatty acid requirements are met

Recommendation

• Low saturated fat diet is desirable

PART 7️⃣ — CARBOHYDRATE: CHEAP ENERGY

Key Features

• Cheapest calorie source
• Supplies ≥50% of calories in most diets

Typical Distribution (Middle-Class American Diet)

• Carbohydrate: ~50%
• Protein: ~15%
• Fat: ~35%

PART 8️⃣ — PRACTICAL DIET CALCULATION LOGIC

Stepwise Method

1. Meet protein requirement first
2. Decide fat intake
3. Fill remaining calories with carbohydrate

Worked Example

65-kg moderately active man

• Total requirement: ~2800 kcal/day
• Protein:
• 65 g/day
• Energy = 65 × 4.1 = 267 kcal
• Some must be Grade I protein
• Fat:
• Reasonable intake: 50–60 g/day
• Remaining calories:
• Supplied by carbohydrate

PART 9️⃣ — MINERAL REQUIREMENTS

General Principle

• Many minerals must be ingested daily
• Includes:
• Major minerals
• Trace elements

Trace Elements

• Defined as elements present in minute tissue amounts
• Essential for life (shown at least in animals)

PART 🔟 — MINERAL DEFICIENCIES: HUMAN EFFECTS

PART 1️⃣1️⃣ — MINERAL EXCESS: TOXICITY

Iron

• Excess → hemochromatosis
• Due to genetic failure of iron absorption regulation

Copper

• Excess → Wilson disease
• Causes brain damage

Sodium & Potassium

• Essential
• Practically unavoidable in diet
• Low-salt diet:
• Well tolerated long-term
• Due to renal Na⁺ conservation mechanisms

PART 1️⃣2️⃣ — VITAMINS: WHY THEY EXIST

Discovery Logic

• Diets adequate in:
• Calories
• Amino acids
• Fats
• Minerals

still failed to maintain health

Definition

• Vitamin = organic dietary substance
• Necessary for:
• Life
• Health
• Growth
• Does NOT supply energy

PART 1️⃣3️⃣ — SPECIES DIFFERENCES

• Some substances:
• Are vitamins in one species
• Not vitamins in another
• Due to metabolic differences

PART 1️⃣4️⃣ — VITAMIN ABSORPTION

Water-Soluble Vitamins

• Vitamin B complex
• Vitamin C
• Easily absorbed

Fat-Soluble Vitamins

• Vitamins A, D, E, K
• Poor absorption if:
• No bile
• No pancreatic enzymes
• Some dietary fat is essential for absorption

Clinical Implication

• Obstructive jaundice
• Pancreatic exocrine disease

→ fat-soluble vitamin deficiency despite adequate intake

PART 1️⃣5️⃣ — VITAMIN TRANSPORT IN BLOOD

• Vitamin A & D:
• Bound to specific transport proteins
• Vitamin E:
• α-tocopherol bound to chylomicrons
• Transferred in liver to VLDL
• Distributed via α-tocopherol transfer protein

Genetic Defect

• Defective α-tocopherol transfer protein:
• Cellular vitamin E deficiency
• Disease resembling Friedreich ataxia

PART 1️⃣6️⃣ — VITAMIN C TRANSPORTERS

• Two Na⁺-dependent L-ascorbic acid transporters:
1. Kidneys, intestines, liver
2. Brain and eyes

PART 1️⃣7️⃣ — VITAMIN DEFICIENCY & TOXICITY

Key Warning

• Fat-soluble vitamin excess is dangerous

Hypervitaminosis A

• Anorexia
• Headache
• Hepatosplenomegaly
• Irritability
• Scaly skin
• Hair loss
• Bone pain
• Hyperostosis
• Acute toxicity described in Arctic explorers after polar bear liver ingestion

Hypervitaminosis D

• Weight loss
• Soft tissue calcification
• Acute kidney injury

Hypervitaminosis K

• GI disturbances
• Anemia

Water-Soluble Vitamins

• Usually excreted
• BUT:
• Megadoses of vitamin B6 (pyridoxine) →
• Peripheral neuropathy

PART 1️⃣8️⃣ — TRACE ELEMENTS (COMPLETE LIST)

Essential trace elements believed necessary for life:

• Arsenic
• Manganese
• Chromium
• Molybdenum
• Cobalt
• Nickel
• Copper
• Selenium
• Fluorine
• Silicon
• Iodine
• Vanadium
• Iron
• Zinc