Physiological Factors Affecting Absorption Through the GIT

1. Surface Area of the Intestine

• Folds of Kerckring - circular folds that increase area by ~3 times
• Villi - tiny finger-like projections that add another 10 times
• Microvilli (Brush Border) - microscopic hair-like structures on each cell that add another 20 times

More surface area = faster and greater absorption.

2. Gastric pH (Acidity/Alkalinity)

• The stomach is very acidic (low pH). Drugs and nutrients that are weak acids (like aspirin) get absorbed well in this acidic environment.
• As food moves to the small intestine, pH rises (becomes more alkaline). Weak bases absorb better here.
• If gastric pH increases (e.g., in older adults or with antacids), the absorption pattern of many substances changes - it can increase for some and decrease for others.

pH determines whether a substance is in an ionized (charged) or non-ionized (uncharged) form. Non-ionized forms cross cell membranes much more easily.

3. Gastric Emptying Rate

• How fast food leaves the stomach and enters the small intestine directly controls how fast absorption begins.
• Slow gastric emptying = absorption is delayed (peak effect of a drug or nutrient comes later)
• Fast gastric emptying = substance reaches the small intestine sooner = faster absorption

4. GI Motility (How Fast Contents Move Through the Gut)

• Motility refers to how quickly the gut moves its contents forward (peristalsis).
• Too fast motility (diarrhea) = contents rush through before absorption can happen = less absorbed
• Too slow motility (constipation or reduced bowel movement) = longer contact time = more absorption

5. Splanchnic Blood Flow (Blood Supply to the Gut)

• The intestines receive a large blood supply. Blood flow to the GI tract can increase up to 8 times after a meal (postprandial hyperemia).
• This increased flow carries absorbed substances away quickly, keeping the concentration gradient steep - which drives more absorption.
• Reduced blood flow (e.g., in shock, heart failure, or older adults) slows absorption because the gradient flattens.

Think of blood flow as the "drainage system." If it drains absorbed substances away fast, more keeps getting pulled across.

6. Site of Absorption in the GIT

7. Presence of Food (Fed vs. Fasted State)

• Food in the stomach affects absorption of drugs and nutrients in many ways:
  • Food stimulates bile and enzyme secretion, which helps digest and absorb fats
  • Some drugs absorb better with food (e.g., fat-soluble vitamins A, D, E, K)
  • Some drugs absorb better on an empty stomach (e.g., certain antibiotics)
  • Food also slows gastric emptying, which delays but sometimes improves absorption

8. Intestinal Fluid Volume and Osmolarity

• Water is absorbed by osmosis - it follows concentration gradients passively.
• If hyperosmotic (very concentrated) solution enters from the stomach, water is actually pulled into the gut lumen from the blood, diluting the contents.
• Once contents become isotonic (same concentration as blood), water and nutrients absorb smoothly.

9. Age-Related Changes (A Special Physiological Factor)

• Gastric pH increases (less acid)
• Gastric emptying slows down
• Splanchnic blood flow decreases
• Bowel motility decreases

Quick Summary Table

Order of Reaction

Zero-Order Reaction (Zero-Order Kinetics)

• The reaction proceeds at a constant rate, no matter how much substance (concentration) is present.
• A fixed amount of drug is eliminated per unit time (e.g., "10 mg eliminated every hour" - always the same amount).
• This happens when the process (enzyme system, transporter, etc.) responsible for elimination becomes saturated - meaning it's already working at full capacity and can't speed up even if there's more drug available.
• Rate equation: dA/dt = -k₀ (rate is constant, independent of concentration)
• Graph: If you plot concentration vs. time, you get a straight line (linear decline).

First-Order Reaction (First-Order Kinetics)

• The reaction rate is proportional to the concentration present at that moment.
• This means: the more drug present, the faster it's eliminated; as concentration drops, the elimination rate also slows down.
• A constant fraction (percentage) of the drug is eliminated per unit time (not a fixed amount) - e.g., "50% eliminated every hour," regardless of how much drug is there.
• Rate equation: dA/dt = -k₁ × A(t) (rate depends on the amount/concentration present)
• Graph: Concentration vs. time gives a curved (exponential) decline; but if you plot the log of concentration vs. time, it becomes a straight line.

Easy Way to Remember the Difference

Simple Analogy

• First-order: If there are only a few cars, they pass through quickly. If there are many cars, the "rate" they can be processed still depends on how many are lined up — more cars waiting, faster overall throughput at the booths (proportional to how many are there), and it slows down as the number of cars decreases. This mirrors how first-order elimination speeds up when concentration is high and slows down as concentration drops.
• Zero-order: The toll booth can only process a fixed number of cars per minute, no matter how many cars are lined up waiting. Even if there's a huge traffic jam (high concentration), the booth still lets through only its maximum fixed capacity. This is exactly what happens when an enzyme system is saturated - it becomes the bottleneck.

Clinical Relevance

• Phenytoin: follows first-order kinetics at therapeutic doses, but shifts to zero-order once the metabolic enzymes are saturated at higher doses.
• Salicylates (aspirin): first-order at therapeutic concentrations, but becomes zero-order once serum levels exceed about 30 mg/dL (toxic range), because metabolic pathways get saturated.