Oral cavity

oropharynx

esophagus

stomachliver

GallbladderSmall intestine

Large intestine

rectum

pancreas

Anal canal

Salivary glands

Accessory OrgansAlimentary Canal

The Alimentary Canals

DIGESTIVE SYSTEM FUNCTIONS

• Obtain nutrients for cells• Nutrients are needed/used for:

– Energy source (break down of nutrients can generate ATP)

– Building materials for:• Cell Growth• Cell Repair• Cell Maintenance• Production of hormones, enzymes, etc….

– Elements for normal cell function• Coenzymes, ions, etc…

D.S. processes• Ingestion—bring nutrients/ food it into our alimentary

canal• Mechanical Digestion

– breaking big into small—no chemical changes– Facilitates chemical digestion

• Chemical Digestion– breaking of covalent bonds by enzymes to turn large molecules

into small molecules (molecules small enough for absorption)

• Absorption:– nutrients cross epithelial tissue of alimentary canal and enter

circulation—cardiovascular or lymphatic systems

• Propulsion—peristalsis– Movement of ingested material made possible by muscle—

mostly smooth—lining digestive tract

• Elimination of material that was not digested or absorbed

Macromolecule Review:these are the major nutrients (i.e., macronutrients)

• Carbohydrates: – monosaccharides < disaccharides < polysaccharides– Amylase = enzymes that break down carbs

• Proteins: – amino acids– Protease = enzymes that break down proteins

• Lipids: – Fatty Acids + Glycerol/monoglycerides– Lipase = enzyme that breaks down lipids

Figure 24.1

1. Liver – Break down and synthesize (interconvert) most carbs, lipids, and

amino acids/proteins– Stores glycogen– ONLY TISSUE THAT CAN RELEASE GLUCOSE*

• When glucose enters non-liver tissue it is phosphoylated preventing it from crossing back out across the PM

• Only the liver can de-phosphorylate

2. Adipose tissue – Stores lipids primarily as triglycerides– Can release lipids as fatty acids and glycerol

*as far as we are concerned.

five metabolic components/tissues

3. Skeletal muscle (close to half your body mass)– Creates substantial glycogen reserves– Proteins in myofibrils can be broken down as source of

releasable amino acids– Uses mostly glucose and triglycerides for energy

4. Neural tissue--BRAIN– Requires glucose* and has high glucose demand– canNOT store energy reserves

5. Other tissues – Insignificant energy reserves– Variable use of carbs, lipids, and amino acids (and

others) substrates.

five metabolic components/tissues

Absorptive State

• 0-4 hrs after feeding• Period of increase blood nutrient levels• Period of increased nutrient availability• Characterized by nutrient uptake by cells• Cells use plasma nutrients as source of energy• Cells generate nutrient stores from uptake of

nutrients• Promoted by insulin

Insulin• Released from beta cells in pancrease• Promotes cell uptake of nutrients from plasma• Reduces blood glucose (lipids & amino acid)• Production of glyocogen (glycogenisis)• Stimulates adipocytes to synthesize triglycerides (with glucose)• Stimulates protein synthesis

Insulin release is stimulated by:• High blood glucose levels• High amino acids levels• Digestive activity

Fate of Nutrients: Absorptive State

* Resting skeletal muscle uses triglycerides for ATP, but

uptakes glucose and stores it as glycogen

*

Absorptive State

LiverG.I. Tract

(small intestines)

Other cells

blood

Stored Substrates

1-2 months of ATP

~4 hrs – overnight worth of ATP -- only liver can release glucose -- muscle glucose cannot be released

Mostly in skeletal muscle

Proteins (amino acids)

14.46%

Mostly in adipose tissue

Post-Absorptive State

• >4 hrs after a meal• Cells use own stored energy reserves• Release of stored reserves into blood• Formation of glucose from non-carbs (gluconeogenisis)

• Glucose sparing • Ensures adequate blood glucose for the brain• Promoted primarily by Glucagon

– Also glucocorticoids, epinephrine, and other hormones

Glucagon

• Released by alpha cells in pancrease• Breakdown of glycogen (glycogenolysis) in liver

and relase of glucose into blood• Stimulates gluconeogenisis in liver and release of

glucose into blood• Stimulates adipocytes to release lipids• Blood fatty acid levels rise

• Glucagon release is stimulated by low blood sugar

Post-Absorptive State & the Brain

• The brain is primarily dependent on glucose• The brain does not store glucose or glycogen• Brain is dependent on constant supply of blood

glucose to function

• Many post-absorptive activities ensure brain has adequate glucose

Post-Absorptive State & the liver

• The liver is the only* organ that has cells which can release glucose

• The liver is the major metabolic organ that can interconvert major macromolecules

• The liver can release stored glucose into blood• The liver can uptake non-carbs, convert them to

glucose (gluconeogenisis), and then release that glucose

Post Absorptive Substrate Fate

Post-absorptive State

LiverG.I. Tract

(small intestines)

blood

Other cells Brain

ATP

Adipose Tissue

MuscleTissue

Liver

Interconversion of substrates:Common source organs/tissues

Insulin release and action

Insulin, Glucagon and Blood Sugar

• Negative Feedback control of blood glucose by insulin and glucagon

Diabetes Mellitus:high blood sugar/inability to regulate blood glucose levels

Types:Type 1 Diabetes (10-15% of diabetes)• usually appears by early adulthood• autoimmune disorder that destroys beta cells• most commonly treated with supplemental insulin and blood glucose

monitoringType 2 Diabetes (85-90% of diabetes)• Cells of body stop responding to insulin (insulin resistance).• Caused largely by lifestyle (poor diet and lack of exercise)• Some ethnicities are more genetically susceptible (will get it faster/easier

and easier in light of poor diet and lack of exercise)– Thrifty Gene Hypothesis

• largely a preventable disorder• Treated with drugs, change in diet, and exercise

Gestational Diabetes:• Can happen during pregnancy

More on Type 2 Diabetes

leading cause of:– amputations– blindness– impotence– heart/cardiovascular disease– hypertension– strokes– renal/kidney failure– slow healing wound/increased risk of infection

• 7th leading cause of death, but contributes to death by renal failure and CV disease (70% of deaths due to diabetes related deaths also had heart disease) (CDC)

• Rate of Type 2 doubled between 1990 and 2005 in the U.S. (CDC)

• Currently 23.2 million in US have it—7.5% of the population….and growing (CDC)

• estimated $1 out of every $8 healthcare dollars spent are diabetes related• $174 billion in diabetes related costs, 116 billion were DIRECT costs. (NIH)

• WITH “typical” health insurance Type 2 diabetes will cost you an average of $1900/yr—with no serious complications (NIH)

Diabetes S/Sx

Primary• Frequent urination• Increase thirst• Increase hunger

other• blurred/diminished vision• acetone/fruity breath• acidosis/metabolic problems with deep labored

breathing….primarily in Type 1

Glucocorticoids (e.g. cortisol)• Released from the andrenal cortex• Increase glucose synthesis in liver (gluconeogenisis)• Causes adipose cells to release fatty acids into blood• Promotes protein breakdown and amino acid release into blood• Inhibits glucose use by organs/tissues other than the brain (spares

glucose for brain)• Causes other tissues to metabolize fatty acids and proteins rather than

glucose for their own needs to “spare” glucose for the brain.• Also anti-inflammatory and inhibits WBC, release of histimine and

reduce the movement of phagocytes to the site generally reducing inflammation but slowing the healing and increasing risk of infection.

Increased levels released in response to stress

(e.g., fasting and physical activity)

Oral Cavity

Oral CavityKey Processes• mastication = mechanical digestion by teeth• chemical digestion

– salivary amylase • Complex carbs disaccharides

– Salivary lipase breaks down lipids

Saliva (from salivary glands)• salivary amylase: breaks down carbohydrates• mucus: holds food together, lubricates• stimulated by parasympathetic ANS

pH of oral cavity is near 7 (more or less neutral)

Esophagus

• A muscular tube that conducts/propells food (bolus) to the stomach.

Stomach Anatomy• Cardiac/Lower Esophageal

Sphincter– prevents movement of stomach

contents back into the esophagus

– heart burn/acid reflux/GERD caused by failure of valve to do its job

• Pyloric Sphincter– regulates the passage of food

into small intestine (emptying of stomach)

• Lined by simple columnar tissue– Thin enough to be readily

permeable– Cells have enough volume to

contain necessary machinery (organelles to make proteins and process energy/ATP)

– Mucus=protects lining of stomach

Hiatal Hernia: the stomach slips up into the thoracic cavity through an

opening in the diaphragm. Promotes reflux.

Stomach Function

• Chemical Digestion of Proteins

• destruction of ingested pathogens

• Minimal absorption – (lipid soluble substances, water, alcohol, some ions)

Gastric Juice

Stomach lining and gastric pits/glands

Gastric JuiceSecreted by Gastric Glands and Contains:• Pepsinogen=inactive enzyme that digests

proteins• Hydrochloric Acid (HCl)

– activates pepsinogen• pepsinogen + HCl pepsin (digestive enzyme)

– creates low pH ~ 2.5 - 4.5• denatures protiens and kills pathogens

• Intrinsic factor (helps absorb B12)• Gastrin a regulatory hormone

Peptic Ulcers:either in stomach (gastric) or duodenum (duodenal)

• 70-90% involve the bacteria Helicobacter pylori

• can be treated with antibiotics

• founders won nobel prize (but not without effort and unconventional demonstrations)

• But 80% of individuals harboring H. pylori are a symptomatic. – Why do only some individuals get ulcers?

Acid Reflux and Hiatal Hernias• Failure of the L.E.S. to work correctly can lead to

acid reflux• Displacement of the L.E.S. relative to the

diaphragm—hiatal hernia--promotes acid reflux because the diaphragm no longer reinforces the L.E.S.– Can also cause breathing difficulty in some settings

• Acid reflux is uncomfortable, can cause histological changes in esophagus, increases likelihood of esophageal cancer, can even cause pneumonia if acids are aspirated

Small Intestines

• THE PRIMARY SITE OF DIGESTION AND ABSORPTION

• Lined with simple columnar cells– thin enough to be

permeable, – big enough to perform

active process such as secretion and absorption

• pH ~ 8 (slightly alkaline/basic)

S.I. Processes

• Chemical Digestion– Receives digestive enzymes from pancreas

and produces own

• Absorption– nutrients cross intestinal wall and enter

circulation

• features that increase absorption– villi, microvilli, length of intestines

Absorption of Nutrients

• monosaccharides blood/capillaries• amino acids blood/capillaries• glycerol/monoglycerides blood capillaries• fatty acids lymph/lacteals

• Hepatic Portal System: nutrients that are absorbed into blood are delivered directly to liver where the liver can remove many nutrients for storage and/or conversion and toxins can be neutralized.

Colon (large intestine)• simple columnar

– (thin enough to be permeable, big enough for active processes)

• Many goblet cells producing lubricating mucus

• Houses normal flora (bacteria)– feed off of material we don’t

digest/absorb– produce vitamins (K and some B

complex vitamins)– produce flatulence—farts– evidence they can influence

adipose tissue/fat deposition– evidence they influence/modulate

our immune system

Processes• Absorption of most remaining

liquid– compacts undigested and

unabsorbed material into feces/poop

Liver Functions• Stores and Releases glucose (only organ/tissue that

can release glucose)– to stabilize blood glucose

• Synthesizes and stores lipids (chlosterol, …..) also regulates circulating lipids– foie gras anyone?

• Amino Acid interconversion and breakdown (gluconeogenisis)

• Detoxify absorbed toxins• Removes old RBC’s• Produces Bile

– bile emulsifies fat (mechanically breaks it up and allows it to mix with water)

– eliminates cholesterol and bilirubin• Bile is stored in gallbladder and enters duodeum

through a system of ducts (biliary ducts)

Pancreas

• Digestive Function– Creates Pancreatic Juice that enters

duodenum– digestive enzymes that breakdown carbs,

lipids, and proteins– alkaline to neutralize stomach acid

• Endocrine Function– releases insulin and glucagon (more later)

Substrate Use:molecules broken down to generate ATP

Two primary molecules used for energy are:• Glucose (carbohydrate)

• can be stored as glycogen by various cells• once glucose enters a cell it cannot leave (except liver)• produces 4 kilocalories of energy per gram• Brain is highly dependent on glucose but can’t store it

• Fats (triglyercides = Fatty acids + glycerol)• Occurs mainly in adipose and liver tissues • Yields 9 kilocalories/g

• Proteins are typically not a primary source of energy

5-35

Uses of Different Energy Sources• Different cells have different preferred energy substrates• Brain uses glucose as its major source of energy

5-48

Interconversion of energy substrates:

excess intake/storage • Excess glucose enters cells and is stored

as glycogen• Once glyocogen stores are maximized

glucose is converted into fats for storage• glucose can even be used to create amino

acids• If you intake more amino acids then

needed they can be converted into glucose and fats/triglycerides

Essential and Non-essential Amino Acids• 20 amino acids are used to build proteins• 12 can be produced by body• 8 must come from diet (= essential amino acids)

5-42

can be synthesized by our body

various intermediate molecules

from diet and absorbed by

digestive system

ATP

Substrate Interconversion

When energy is needed:• Glucose and Fats (both stored and circulating)

can be broken down through cellular respirationIf more glucose is needed:• stored glycogen is broken downWhen cells use up their stored substrates:• adipocytes and release lipids into blood• liver can release its stored carbohydrates• fats and amino acids can be converted into the

carbs (gluconeogenisis)– Particularly important to keep the brain functioning

various intermediate molecules

sources of energy for a

cell

ATP

Insulin and Glucagon:Hormones release by Pancreas

Insulin:• released by beta cells in pancreas in response to high

blood glucose

• lowers blood glucose levels by stimulating liver to remove glucose and create glycogen

• promotes uptake (by facilitated diffusion) of glucose by cells of body)

• Also stimulates update of amino acids and production of proteins and uptake and synthesis of fats (including by adipocytes)

Insulin and Glucagon:Hormones release by Pancreas

Glucagon• released by alpha cells in pancreas in response to low

blood glucose

• Promotes glucose synthesis (from glycogen and other) and release by the liver

• stimulates the breakdown and release of fats/lipids by adipocytes