Lectures 29-30: Human Physiology 3

Essential nutrients

Required materials that cannot be synthesised by animals

Classes of essential nutrients

Essential amino acids

Essential fatty acids

Vitamins

Minerals

Linoleic acid

Essential fatty acid

Converted into γ-linoleic acid via fatty acid desaturase

γ-linoleic acid

Precursor for phospholipids & prostaglandins

Food processing

Ingestion

Digestion

Absorption

Elimination

Digestion

Mechanical & chemical

Breaking down food small enough to absorb

Mechanical digestion

Chewing & grinding food

Increases surface area of food

Chemical digestion

Splits food into molecules small enough to pass through membrane

Used to make larger molecules

Splits bonds of molecules via enzymatic hydrolysis & water

Digestive system organs

Tongue & oral cavity

Pharynx & esophagus

Stomach

Small & large intestine

Rectum

Anus

Digestive system accessory glands (mammals)

Secretes digestive juices into alimentary canal

Salivary glands

Pancreas

Liver

Gallbladder

Saliva

Exocrine secretion from salivary glands

Mucus, water, salts, cells, glycoproteins, amylase

Amylase

Breaks down starches

Tongue in digestion

Shapes food into bolus (ball shape) to help swallow

Pharynx

Connects mouth to esophagus & trachea

Esophagus

Connects to stomach

Swallowing

Epiglottis blocks entry to trachea

Larynx (upper respiratory tract) guides bolus

Coughing & digestion

Swallowing reflex fails

Food or liquid reaches trachea

Esophagus open

Epiglottis goes down

Esophageal sphincter relaxes

Trachea open

Esophageal sphincter contracted

Epiglottis up

Peristalsis

Rhythmic contractions of canal wall muscles

Pharynx → stomach

Small intestine

Large intestine

Sphincters

Valves

Regulate movement of material between compartments

Digestive tract wall layers

Lumen (inner) - ducts from glands go into lumen

Mucose

Submucosa

Submucosal plexus

Myenteric plexus

Muscularis externa

Serosa

Mesentery

Peritoneum

Body wall

Mucosa contents

Mucous membrane

Lamina propria

Muscularis mucosa

Muscularis externa contents

Outer longitudinal muscle

Inner circular muscle

Stomach digestion

Stores & processes food into liquid suspension

Mechanical: churning via muscle contractions

Chemical: secretes gastric juice

Gastric juice

Low pH (2), kills bacteria & denatures protein

Hydrochloric acid (HCl) & pepsin

Pepsin

Protease

Breaks peptide bonds to cleave proteins into smaller peptides

Gastric juice synthesis

Hydrogen & chloride ions secreted to lumen via parietal cells

Chief cells secrete inactive pepsinogen into lumen

HCl converts inactive pepsinogen → active pepsin

Pepsin activates more pepsinogen → chain reaction

Chyme

Mixture of ingested food & gastric juice

Mucus in stomach

Protects stomach lining from gastric juice

New epithelial layer every 3 days

Gastric ulcers

Lesions in stomach lining

Caused by helicobacter pylori (bacteria)

Nobel prize in 2005 for physiology or medicine

Small intestine

Longest compartment of alimentary canal

Large surface area due to villi & microvilli in intestinal lumen

1 duodenum

2 jejunum

3 ileum

Alimentary canal

Entire passage that food goes through during digestion

Mouth → anus

Small intestine digestion

Enzymatic hydrolysis of food macromolecules

Digestion in duodenum

Chyme from stomach mixes w/ pancreas, liver, gallbladder & small intestine juices

Activates trypsin & chymotrypsin in lumen

Neutralises acidic chyme via alkaline solution in duodenum

Trypsin & chymotrypsin

Proteases synthesised in pancreas

Activated in duodenum lumen

Bile salts

Aids digestion of fats

Major component of bile

Bile

Made in liver

Stored in gallbladder

Digestion of fats (salts)

Destroys nonfunctional red blood cells

Microvilli in intestines

Creates brush border

Increases rate of nutrient absorption

Small intestine absoption

Most water ingested is absorbed in small intestine via osmosis

Villi & microvilli increase nutrient absorption rate

Passive or active transport (nutrient dependent) across epithelial cells

Amino acids & sugars → blood

Fatty acids & monoglycerides → fats → lymph

Villi structure

Epithelial cell lining

Lacteal w/ blood capillaries

Hepatic portal vein

Carries nutrient rich blood from villi capillaries → liver → heart → other organs

Liver in digestion

Regulates nutrient distribution

Interconverts organic molecules

Detoxifies organic molecules

Fat digestion & absorption

In small intestine lumen:

Bile salts break up fat globules → triglycerides more exposed to hydrolysis

Triglycerides broken down into fatty acids & monoglycerides via lipase

In epithelial cell:

Monoglycerides & FAs re-formed into triglycerides

TGs coated w/ phospholipids, cholesterol & proteins → chylomicrons (water-soluble particles)

Chylomicrons → lacteal (lymphatic vessel in each villi)

Lymphatic vessels transport lymph w/ chylomicron to large veins → heart

Large intestine

Large intestine canal

Colon

Caecum

Rectum

Caecum

Aids in fermenting plant material

Connects small & large intestine

Appendix

Extends from caecum

Role in immunity

Colon

Leads to rectum & anus

Recovers water (begins in small intestine)

Feces becomes more solid moving through colon

Rectum & anus

Stores feces until can be eliminated via anus

Movements between rectum & anus controlled by 2 sphincters

Polysaccharides digestion

Starch & glycogen

Oral cavity, pharynx & esophagus

Broken down into maltose & smaller polysaccharides via salivary amylase

Disaccharides digestion

Sucrose, lactose, maltose

In small intestine

Broken down into monosaccharides via intestinal epithelium enzymes

Smaller polysaccharides digestion

In small intestine

Broken down into disaccharides via pancreatic amylases

Protein digestion in stomach

Protein → small polypeptides via pepsin

Protein digestion in small intestine

Small polypeptides → smaller polypeptides via trypsin & chymotrypsin

Polypeptides → peptides via pancreatic carboxypeptidase

Peptides → amino acids via dipeptidases, carboxypeptidase & aminopeptidase

Nucleic acid digestion in small intestine

DNA/RNA → nucleotides via pancreatic nucleases

Nucleotides → nucleosides via nucleotidases

Nucleosides → nitrogenous bases, sugars, phosphates via nucleosidases & phosphatases

Fat digestion in small intestine

Triglycerides → glycerol, FAs, monoglycerides via pancreatic lipase

Digestion steps

1 Oral cavity via salivary gland secretions (mechanic & chemical)

2 Esophagus

3 Stomach via gastric juice (mechanical & chemical)

4 Small intestine via liver & pancreas secretions

Absorption steps

1 Small intestine: lipids → lymphatic system → vein → heart

2 Small intestine: → other nutrients → hepatic portal vein → liver → heart

3 Large intestine: water → hepatic portal vein

Excretion steps

Large intestine → colon (water absorption solidifies feces) → rectum → anus

Digestive system regulation via nervous system

Salivary secretion

Cerebral cortex + pressure & chemoreceptors in mouth → salivary centre in medulla → autonomic nerves → salivary glands → increased salivary secretion

Digestive system regulation via endocrine system

Gastrin stimulates gastric juice production

CCK stimulates digestive enzyme & bile release

Secretin stimulates bicarbonate release to neutralise acids

Secretin & CCK inhibit gastric juice secretion & peristalsis to slow digestion when chyme is high in fat

Amino acid absorption pathways

Sent to urea for urinary excretion

Made into body (structural/secretory) proteins

Made into FAs & glucose

Broken down into fuel

Glucose absorption pathways

Made into glycogen to store in liver & muscle

Broken down & used as fuel

Fatty acid absorption pathways

Made into triglycerides for adipose tissue storage

Used for fuel

Food breakdown

Protein → amino acids

Carbohydrates → glucose

Triglyceride fats → fatty acids & monoglycerides

Carbohydrate storage

Circulates as glucose

Stored as glycogen in liver & muscle

1% (1500 cal) of body energy

Less than a day worth of energy

1st energy source

Essential for brain

Fat storage

Circulates as free fatty acids

Stored as triglycerides in adipose tissue

77% (143000 cal) of body energy content

2 months worth of energy

Primary energy reserve

Energy source during fasting

Protein storage

Circulates as amino acids

Stored as body proteins in muscle

22% (41000 cal) of body energy content

Death before reservoir used (structural/functional impairment)

Glucose source for brain

Last resort to meet energy needs

Absorptive state

Fed

Abundant glucose as main energy source

Glycogen & triglyceride synthesis & storage

Protein synthesis

Insulin

Postabsorptive state

Fasting

Endogenous energy stores mobilised for energy

Glycogen degradation & depletion

Glucose conserved for brain

Gluconeogenesis via amino acids

FAs for non-glucose-dependent tissues

Glucagon

Glucagon & insulin

Both synthesised in islets of pancreas

α = glucagon

β = insulin

Regulates glycogen breakdown into glucose

Insulin lowers blood-glucose levels

Glucagon raises blood-glucose levels

Glucose uptake in brain

Brain cells can uptake glucose regardless of insulin presence

Metabolic syndrome

Cluster of related risk factors

Visceral adiposity, insulin resistance, hypertension, high triglycerides, low high-density lipoprotein (HDL) cholesterol

Increases risk of type II diabetes & cardiovascular disease

Chronic state of inflammation = central mechanism underlying insulin resistance

Excess energy & obesity affects

Elevated blood pressure

Prothromobtic state

Insulin resistance & hyperglycemia

Proinflammatory state

Atherogenic dyslipidemia

Metabolic syndrome diagnosis

Waist circumference greater than 102cm (males) & 88cm (females)

High triglycerides - 150 mg/dL (1.7 mmol/L)

Low HDL cholesterol - 40 mg/dL (males) & 50 mg/dL (females)

High BP - higher than 130 (sys) & 85 (dia)

High fasting glucose - 100 mg/dL

Obesity affects

Type 2 diabetes

Colon & breast cancer

Heart attack

Stroke

Ghrenlin

Hormone secreted by stomach wall

Triggers feeling of hunger before meals

PYY

Hormone secreted by small intestine after meals

PYY & insulin suppress appetite

Leptin

Produced by adipose tissue

Suppresses appetite

Regulates body fat levels

GLP-1

Secreted by ileocolonic cells

Triggers insulin release from pancreas

GIP

Secreted by duodenojejunal cells

Primes β-cells for insulin secretion

GLP-1/GIP receptor agonists

Diabetes drugs (ozempic, victoza, mounjaro)

Brain: increased satiety

Pancreas: increased β-cell proliferation & insulin release; decreased β-cell apoptosis & glucagon release

Adipose: increased lipolysis & decreases ectopic fat deposition

Stomach: decreased gastric secretions & emptying

Intestines: decreased gastrointestinal motility

Gut & brain interaction studies

Gut microbiota & brain communication → behaviour modulation

Enteric microbiota interact w/ host & modulate homeostasis

Pre/pro/antibiotics affects gut → stress to brain → subjective responses

Stressor responses

All stressors induce the same general nervous & endocrine response

Acute stress response - helps body cope w/ stressor

Chronic stress - damaging

Hypothalamus pituitary adrenal (HPA) axis

Adrenal medulla & adrenal cortex

Adrenal medulla stress response

Epinephrine & noradrenaline

Glycogen → glucose (increased blood glucose)

Increased BP, breathing rate, metabolic rate

Changed blood flow patterns → increased alertness, decreased digestive, excretory & reproductive system activity

Adrenal cortex stress response

Mineralcorticoids:

Sodium ions & water retention by kidneys

Increased blood volume & pressure

Glucocorticoids:
Protein & fat breakdown into glucose (increased blood glucose)

Partial immune system suppression

Glucocorticoid drugs

Steroids

Partial suppression of immune system

Prescribed for autoimmune disorders, allergies & after organ transplants

Adrenal medulla stimulation

Stress → nerve impulses → spinal cord → nerve impulses → adrenal medulla

Adrenal cortex stimulation

Stress → hypothalamus releases ACTH in anterior pituitary → circulates blood → adrenal cortex

Sedentary behaviour

Waking activity w/ energy expenditure less than or equal to 1.5 metabolic equivalents (MET) and a sitting or reclining posture

Damaging to health

Hazard ratio (95% Cl)

Increases w/ decrease in MET

Exercise & disease

Decreases risk for:

Coronary heart disease, stroke, cancer, type II diabetes, dementia, depression, other heart diseases

Exercise & upper respiratory tract infections

Anti-inflammatory

Sedentary: increased risk of infection

Moderate: lowest risk

High: highest risk

Exercise benefits

Neuro: decreased anxiety, depression, stroke & dementia; increased cognition

Endocrine: decreased weight, diabetes, LDLs; increased HDLs

Musculoskel: decreased osteoporosis, falls, disability

Onco: decreased prostate, breast & bowel cancer

CV: decreased mortality, coronary artery disease, blood pressure

Exercise anti-inflammation in brain

Brain → HPA axis & sympathetic adrenal-medullary axis → adrenal medulla & cortex → increased adrenaline & cortisol → decreased TNF in monocyte

Exercise anti-inflammation in muscle

Muscle → IL-6 → decreased TNF & increased IL-1RA in monocyte

IL-6 → increased IL-1RA & IL-10 in macrophage

IL-6 → increased adrenaline & cortisol in brain

Exercise anti-inflammation in adipose

Decreased M1 macrophages → decreased IL-6 & TNF

Increased M2 macrophages → increased IL-10 & adiponectin

Increased fat mobilisation

Decreased adipocyte size

Exercise anti-inflammation in lymphoid organs

Increased CD4+ T(reg) cells → increased IL-10 in T(reg) cells

Decreased chemokine receptor expression on T cells & monocytes → decreased TLR expression & CD14low CD16+ to CD14high CD16- subset ratio in monocytes

Inflammation effects

Increased IL-6 & TNF, TGs, LDL, free FAs, TLR expression →

Chronic low-grade inflammation

Increased risk for etherosclerosis, T2D, neurodegeneration, tumour growth

Reduced functional capacity & longevity