LECTURE 3

Basis of a Healthy Diet:

• It's important to have the right balance of nutrients in our diet to avoid metabolic disorders like diabetes and heart disease.

• An adult typically needs around 2300 kilocalories per day, with variations based on gender, lifestyle, and life stage. Athletes and pregnant individuals may require more calories due to higher energy expenditure.

• Besides providing energy, our diet also supplies essential nutrients like water, vitamins, and minerals.

• These non-caloric nutrients play vital roles in our body, such as aiding in blood clotting and muscle function.

• Maintaining a proper energy balance is crucial to avoid weight gain or loss. If your energy intake exceeds your expenditure, you'll gain weight, while insufficient intake can lead to weight loss. It's all about finding that right balance for a healthy lifestyle.

• When we talk about carbohydrates, we have simple sugars like glucose and fructose, which can join together to form compounds like sucrose and lactose.

• Our diet also includes polysaccharides like starch and glycogen, which serve as storage molecules. In terms of digestion, amylases help break down these structures into smaller components.

• Proteins are made up of amino acids linked by peptide bonds. There are 20 different amino acids, with 9 essential ones that humans can't produce themselves.

• Daily protein intake should be around 1 gram per kilogram of body weight. Proteins from meat, fish, dairy, and eggs provide the right balance of amino acids, while plant proteins may require larger quantities for the same effect.

• It's important to find the right balance as excessive protein intake can have negative effects on digestion.

• Consuming too much protein can lead to digestive problems like bloating, gas, and constipation. It can also put strain on the kidneys and may increase the risk of osteoporosis.

Fats →

• Fats are made up of triglycerides and cholesterol.

• Triglycerides have a glycerol backbone and three fatty acid side chains.

• When broken down by lipases, they split into glycerol and fatty acids.

• Fats act as storage molecules and insulation in both plants and animals.

• Fatty acids can be saturated (without double bonds) or unsaturated (with double bonds).

• Saturated fats are considered less healthy as they raise LDL cholesterol, while unsaturated fats can lower it.

• Cholesterol is crucial for cell membrane fluidity and steroid hormone production. Most fatty acids can be made by the body, except for essential ones like linoleic acid and linolenic acid.

• Linoleic acid is necessary for arachidonic acid production, which forms inflammatory mediators. Linolenic acid, on the other hand, inhibits inflammatory enzyme production, showing anti-inflammatory properties.

Process of digestion:

• Starting from the mouth where mechanical digestion begins with chewing and swallowing food. Mucosal layer surrounded by layers of smooth muscle to propel it along the tube.

• The food then moves through the esophagus to the stomach, which acts as a storage organ. Digestion and absorption mainly occur in the small intestine, aided by secretions from the pancreas and bile.

• Majority of absorption occurs in the duodenum and jejunum, aided by pancreatic juice + bile.

• The large intestine acts as a storage organ for undigested material as food passes more slowly and absorbs water before passing waste out through the rectum. The transit time from the mouth to the anus can vary, affecting absorption and leading to diarrhea or constipation.

• Overall, digestion involves breaking down large molecules for absorption. The GI tract has functions related to digestion, storage, and absorption.

• If food passes too slowly then that results in constipation and too fast is diarrhea.

Chemical Breakdown of Food:

- Chemical breakdown is part of the digestive process, increasing surface area for enzymes to act on food.

- Food needs to be mixed with acid in the stomach for digestion.

- Stomach provides optimal conditions for enzymatic action.

- Acid in the stomach creates a hostile environment for microbes, acting as a barrier to harmful organisms.

- Optimal conditions in the small intestine are needed for absorption of nutrients and water.

- Water consumption mainly comes from food, and the body is designed to maximize absorption.

- Muscular movements help move food towards the anus for elimination.

- Indigestible or toxic material is released quickly.

- Mechanical digestion starts in the mouth, with important joints like the temporomandibular joint allowing for jaw movements.

- Teeth and jaw are designed to fit together for effective chewing and grinding of food.

- Overhang of the jaw allows lower jaw movement.

- Mastication grinds food with the help of periodontal ligaments.

- Alveolar socket provides cushioning for lateral impact.

- Masseter and temporalis muscles apply force for chewing.

- Tongue shapes food into a bolus, mixes with mucus and saliva for swallowing

Saliva:

• Saliva is composed largely of water.

• It's also contains proteins such as mucins which are slippery. So that provides lubrication and that's also important for speech and swallowing.

• Alpha amylase breaks starting down the digestive process breaking down carbohydrates into simple sugars and antibacterials agents. So mainly lysis.

• Important for the prevention of tooth decay.

• Growth factors → important for repair of the mucosa because it's easily damaged, ions like sodium chloride, calcium and phosphates for repairing the teeth

• fluoride is important for strengthening teeth.

• PH is slightly acidic + saliva is also hypotonic to improve taste.

The three types of salivary glands:

• The parotid glands are in front of the ears and produce a watery secretion.

• The submandibular glands, located underneath the jaw, produce most of the saliva.

• The sublingual glands, under the tongue, produce mucus.

• The saliva glands have acini that look like grapes, which produce an isotonic fluid.

• The saliva composition is determined by how fast it passes through the glands.

• On average, a person produces between 1 and 1.5 liters of saliva per day, and this process is controlled by the autonomic system.

Saliva Production:

• Saliva production is controlled by both the parasympathetic and sympathetic systems.

• Parasympathetic control increases blood flow and produces watery saliva, while sympathetic control leads to thicker, enzyme-rich saliva.

• Nervousness can cause dry mouth due to sympathetic control. Conditions like Sjogren's syndrome → Autoimmune disease in which the immune system produces antibodies against glans like the salivary glands.

• Certain medications can also result in a dry mouth → like sympathetically acting drugs or parasympathetic agonists like atropine.

Saliva secretion:

• Sodium-potassium exchange pump plays a crucial role.

• This pump helps move sodium out of the cell into the blood on one side, while bringing potassium in.

• This action creates a sodium gradient that allows sodium to passively diffuse along with chloride ions, as well as potassium.

• The chloride ions then move across the cell membrane using specific channels like the cystic fibrosis transmembrane regulator and calcium-activated chloride channels.

• This whole process not only affects the cell's membrane potential but also sets up an electrochemical gradient for sodium to move passively between the cells, contributing to the production of saliva.

Aquaporin 5:

• Protein involved in allowing the passage of water.

• When sympathetic stimulation occurs, this protein is inserted into the apical membrane, as observed in experiments on mice.

• Knocking out Aquaporin 5 in mice has shown to reduce saliva production.

• In humans, there are specific receptors that, when activated, increase intracellular calcium levels, leading to further chloride exit and a decrease in membrane potential.

• This process drives more sodium and water across the membrane, ultimately increasing the rate of saliva flow.

Stomach:

• Stomach is divided into different parts, like the fundus and the body, which is the main storage area.

• The three layers of smooth muscle in the stomach, including circular, longitudinal, and oblique muscles, allow for the churning action that mixes food with the stomach acid, turning it into chyme.

• Peristalsis waves push the chyme towards the pylorus, where the more liquid part is pushed down.

• The pyloric sphincter controls the amount of chyme entering the duodenum to maintain the pH balance.

• This process is regulated to prevent excessive acid from entering the duodenum and disrupting the pH balance.

Mechanisms of Absorption:

• About 8 to 10 liters of fluid go into the body per day, with most of it being reabsorbed in the small intestine, and a bit more in the large intestine.

• We typically lose around 100 milliliters of fluid per day.

• The mouth helps break down food mechanically and increase the surface area for digestion.

• When it comes to absorption, very little happens in the stomach due to most molecules being polar and unable to diffuse across the stomach lining.

• However, some exceptions like aspirin, other drugs, and alcohol can be absorbed in the stomach.

• Aspirin, for instance, can provide quick relief but may also damage the stomach lining.

• To prevent this, aspirin can be enteric-coated to be absorbed in the small intestine instead.

Instead:

• Jejunum and ileum are the main spots for absorbing simple sugars, amino acids, and fatty acids.

• The ileum helps with anything that wasn't digested in the duodenum and jejunum.

• It's crucial for absorbing vitamin B12 and bile salts.

• There's active reabsorption of sodium and water, and short-chain fatty acids are produced in the colon, providing fuel for sodium and water transport.

• The rectum allows for drug administration without digestion, as drugs are absorbed quickly without passing through first-pass metabolism.

• It's a handy way to deliver drugs efficiently.

Nutrient Absorption:

• Nutrient absorption, we can split them into polar molecules and lipid-soluble ones.

• Polar molecules like water-soluble monosaccharides, amino acids, ions, and some vitamins need active transport with sodium chloride and bicarbonate.

• The small intestine, being around 6.27 meters long, has folds and villi that increase its surface area for absorption.

• This structure is like a concertina with circular folds and finger-like projections called Villi, enhancing absorption.

Villi:

• If focus on one of those Villi, we can see they're divided into microvilli, forming the brush border of the small intestine.

• Fluids pass through these tiny structures, maintaining contact with the gut's surface.

• The total area, if spread out, would be around 300 square meters, providing ample space for absorption.

• Additionally, the small intestine has a rich blood supply, ensuring a constant concentration gradient and various tools involved in absorption of fatty acids.

Potential routes of absorption:

• When it comes to absorption, fats can diffuse across the cell membrane through simple diffusion.

• On the other hand, amino acids and sugars, being polarized structures, need a carrier to transport them across the cell membrane.

• When it comes to endocytosis, like with vitamin D and intrinsic factor, the cell membrane envelops the material to be transported.

• By forming a circle around it, the material can enter the cell. This is how Vitamin B and intrinsic factor are typically absorbed in humans.

How ions are Absorbed:

• When it comes to absorption, sodium is absorbed primarily through the sodium proton exchanger, which is electro neutral, both positively charged.

• There are three NHE isoforms - NHE 2, NHE 3, and NHE 8. Mutations in the genes producing these can lead to congenital sodium diarrhea and microbial dysbiosis.

• These mutations can also cause inflammation of the gut, contributing to conditions like IBS. Additionally, chloride is absorbed passively down its concentration gradient, and chloride and bicarbonate exchange is coupled to the sodium proton exchanger.

• Mutations in chloride transporter genes can lead to congenital chloride-induced diarrhea.

• Short-chain fatty acids enhance sodium proton exchange and provide an energy source.

• The MCT1 gene is thought to contribute to inflammatory bowel disease. The transporters rely on the dissociation of carbonic acid, catalyzed by carbonic anhydrase, to drive the transport of protons and bicarbonate.

• The CFTR channel is involved in moving sodium and chloride out of the cell, while the epithelial sodium channel transporter helps reabsorb sodium in the colon.

Glucose Transport:

• Glucose and galactose are transported into the blood by the SGLT1 transporter.

• When there's a genetic mutation causing a lack of SGLT1, it leads to glucose and galactose not being transported properly, resulting in diarrhea and dehydration.

• In such cases, patients might need to avoid consuming glucose and galactose and opt for fructose instead, as it's transported differently.

• Amino acids and peptides are absorbed through specialized membrane transporters, depending on the type of amino acid.

• The neutral ones use the MBB transporter, while acidic and basic ones have different transporters. Most of these are linked to sodium transport, and some, like proline and glycine, are coupled to proton gradients.

Small Intestine:

Absorption process of small peptides, fats, and fat-soluble vitamins in the small intestine →

• The breakdown of fat globules with bile salts, emulsification, and the absorption of fatty acids and monoglycerides through diffusion are crucial steps in this process.

• The packaging of these substances into chylomicrons and their transport through the lymphatic system play a significant role in their utilization in the body.

• Additionally, specific proteins and transporters like CD36, LFA BP, and MTPC1L1 help facilitate the transport of fatty acids and cholesterol.

• This process is essential for the absorption of fat-soluble vitamins like A, D, E, and K.

• Most water is absorbed in the small intestine → Most of the water is absorbed in the small intestine because it travels down its osmotic gradient, mainly created by the absorption of nutrients.

• This process allows for the reabsorption of most of the water in the small intestine.

Large Intestine:

• The large intestine's main job is to store fecal material.

• It's full of microbes that help in making vitamin K and also aid in the absorption of sodium and water through the epithelial sodium channel.

• About 30% of feces is made up of microbes. Food spends more time in the large intestine than in the small intestine, around 12 to 18 hours compared to five to six hours.

• The movement of food in the large intestine is helped by mucus and strong contractions that push the feces towards the rectum.

• When pressure increases due to peristalsis and contractions, the internal anal sphincter relaxes, and if the external sphincter also relaxes, that's when defecation happens.