Physiology Supplement

INTRODUCTION –Function (physiology) of Animals

Physiology -study of the mechanisms by which the body functions

Physical external environment (effects of altitude, pressure, temp., etc.)

Homeostasis -maintenance of a constant internal environment, accomplished by reflex arcs which monitor deviations from a set point for a particular variable (i.e. temperature, BP, etc.); carried out mostly by nervous and endocrine systems

Reflex -is usually a built-in response to a stimulus (which is any detectable change in the environment):

Stimulus  Receptor (sensor)  afferent path  Integrating Center

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    | (usually negative) |  

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  Response  Effector (muscle or glands)    efferent path

Negative Feedback -response which opposes the stimulus (most common)

Positive Feedback -response which increases the stimulus further

Most parameters in the body are controlled by several effectors operating antagonistically to one another

Factors which affect Homeostasis:

1. Feed-forward regulation -anticipates changes in the environment and responds before the change actually occurs

2. Acclimatization -enhancement of response due to prolonged exposure

3. Biorhythms -internally driven cycles

External Environment

• Atmosphere
  Composition (Dry air): 78% N₂, 20% O₂, 0.3% CO₂

• Pressure at sea level = 760 mm Hg = 101kPa = 1 atm

• Partial Pressure(PP)(g) = Fracitional Composition (%) * Total Press.

• PP _H2O reduces PP (by decreasing the fraction composition) of other gases

• Pressure declines by ½ for each 5500 m increase in altitude; as does PP

• Temperature range = -70 to 50⁰C; low heat capacity

• Temperature decreases 6-10^oC per 1000m increase in altitude

• Aquatic Environments

• Salinity:  Fresh water = 0-0.5%; Brackish waters = 0.5-30%; Sea water = 30-40%
  Hypersaline water (such as salt lakes) >40%

• Ionic composition is very variable (Major ions are Na and Cl, minor Ca, Mg, SO₄ and others)

• Dissolved gas varies with PP, solubility of the gas, the salinity and temperature of the water; it also tends to decrease with depth (ocean dissolved O₂ is 1-6 ml/L)

• Temperature (0-100^oC) solutes may lower freezing point (FP for ocean water is -2⁰C), boiling point may be greatly elevated by solutes and increased pressure found in subterranean and submarine environments.  Temperature in water is generally stratified, with the most dense water (4⁰C) at the bottom

• Mean depth of the ocean = 3800m   Max = 10000m

• Pressure increases one atmosphere per 10 m of depth; can compress air spaces in bodies and alter ionization of water, protein structure and enzyme function

• Light usually totally absorbed by 8m of depth (>90% absorption) depending water clarity; red light absorbed the most, blue the least

• Terrestrial Environments –classified as biomes (water abundance, temperature or dominant community type)

• water abundance determined annual precipitation, evapotranspiration ratio, and humidity

• can be greatly affected by local preturbances (mountain shadow, altitude, ocean currents, solar radiation)

• Subterranean environments may have lower O₂ and higher CO₂ due to animal metabolism and microorganism activity

Internal Environment

• 60-90% water, 18% protein, 15% fat, 7% mineral of body weight

• 63% hydrogen, 25% oxygen, 9.5% carbon, 1.4 % nitrogen (=99%)

• <1% Minor elements: Ca, P, Cl, K, S, Na, Mg

• Trace elements (<0.01%): Fe, Fl, Zn, I, Co, Mn, Cr

Body Fluid Compartments

Extracellular fluid (ECF): that fluid contained within the skin but external to cells; makes up about 1/3 of the total body water (20% total body weight)

A.  Interstitial fluid -that fluid bathing all cells outside of the bloodstream; 15% body weight

B.  Blood Plasma -the fluid component of the bloodstream; 5% body weight

C.  Transcellular fluids -fluids which appear to be outside but connected to the ECF; such as: CSF, fluids in the eye, glandular secretions, etc.  (very small quantities)

Intracellular fluid -fluid found within cell membranes; makes up 2/3 of the total body water; 40% of body weight

Dissolution of substance in a body fluid can be used to calculate the volume of fluid.   

(Amount of substance injected – amount lost or metabolized)/concentration found in the fluid = volume of compartments the substance entered

To measure ECF (inject substance which can mix into compartment subtract the amount excreted or metabolized and divide by the concentration found in the plasma.

Given a 150 mg of sucrose was injected into a 70 Kg man.  The man excreted 10 mg sucrose and the plasma concentration was 0.01 mg/ml

(150-10)/0.01 = 14000ml ECFOrganization of the Body:

Cells -basic unit of life

Tissues -aggregates of cells with similar characteristics

Organs -combinations of tissues to perform a specific function

Organ Systems -combinations of organs to perform some overall function

Tissues: are a group of similar cells and their associated extracellular substances which carry out a specific task.  Four basic types: Epithelium, Muscle, Nervous, CT.

Digestive System

Digestion - reduction through hydrolysis of complex food substances into simpler monomers 

Functions of digestive system:

1. Motility

• ingestion -intake of food into GI tract

• transportation of food through system by peristalsis

• mastication -chewing

• deglutition -swallowing

• mixing by segmentation and churning

• egestion -defecation

1. Secretion
   exocrine: secretion of products to aid in digestion
   like: HCl, water, bicarbonate, enzymes

endocrine: secretion of hormones to regulate GI tract

1. Digestion - mechanical (includes grinding, mixing, liquefying) and chemical breakdown of food into small particles

2. Absorption - passage of particles from external to internal environment

Major Organs (alimentary canal or GI tract)

- mouth, pharynx, esophagus, stomach, small intestine, large intestine, rectum, and anus

Accessory organs

-teeth, tongue, salivary glands, liver, gall bladder, and pancreas

Basic Layers of Tubes of GI tract:

1. Mucosa -epithelium (usually simple columnar) and its basement membrane

2. Submucosa -CT layer with glands, blood and lymphatic vessels, and nerves

3. Muscularis -large smooth muscle layer with at least two layers, an outer longitudinal and an inner circular layer

4. Serosa or Adventitia -mostly the serosa is a mesothelium continuous with mesenteries but may be just CT where the tubes lie behind body cavity linings

Mouth - for ingestion generates the food bolus

Tongue - involved in mechanical digestion and taste

Salivary glands (parotid, submandibular, sublingual) saliva - 99% water + electrolytes

-also mucus and digestive enzymes => salivary amylase (ptyalin) (breaks down starch), maltase

Teeth - mechanical digestion (mastication)

 -therefore: the mouth mechanically digests food, hydrates food with a very limited amount of chemical dig.

Pharynx - swallowing (deglutition)

 - junction area of oral and nasal cavities, esophagus and trachea

Esophagus - transports food to stomach (deglutition)

 Function: - actively transports food via peristalsis

Stomach: - muscular pouch which receives bolus and delivers chyme (liquefies food)

Function - food storage and mechanical digestion (with some chemical)

Anatomy - rugae present (temporary foldings in mucosa layer)

- simple columnar epithelium with openings (gastric pits) leading to the gastric glands

  -Gastric glands: -secrete gastric juice which consists of the following secretions: water, mucus, pepsinogen (inactive enzyme which activates in acid to pepsin which catalyzes breakdown of proteins to peptides), rennin (coagulates milk), HCl, gastric intrinsic factor

Small Intestine (duodenum, jejunum, ileum)

- largest amount of digestion and absorption

- structures to increase surface area

1. plica circularis - permanent foldings of the mucosa and submucosa

2. villi - finger-like protrusions of the mucosa (epithelium and lamina propria) contains BV and lacteal

3. microvilli - microscopic protrusions of the cell membrane from each epithelial cell creates an undisturbed brush border with embedded enzymes (ex. Enterokinase, many others)

4. increase length - the small intestine is the longest segment of the digestive tract (6 ft in life; 18-20 ft in cadavers)

- mucosa has pits like stomach = crypts of Lieberkuhn (intestinal glands) which secrete intestinal juice; each gland secretes mucus, antibacterial compounds, and enzymes

Large Intestine functions:

- absorption of water and electrolytes; receives 1.5-2L of water a day and absorbs 90% of it; less than 200ml of water excreted with feces. Absorption of water accomplished by membrane pumps located in basolateral membrane of epithelium which create an osmotic gradient.  

- egestion

- limited amount of absorption; no digestion other than continuation of reactions started in small intestine

Liver - developed from outpocket of GI tract: functions:

- metabolism of all three basic food types

- storage of Fe and Cu and glycogen

- storage of Vit. A, B12, D, E, and K

- production of plasma proteins (albumin, clotting factors, heparin, etc.)

- bile production (emulsifies fats) in intestine

- detoxifies the blood and can store toxins

Gall Bladder - develops from ducts of liver; function: storage and concentration of bile

Pancreas

-heterocrine gland - both exocrine and endocrine

 - exocrine - secretes product into ducts: pancreatic juice (juice consists of sodium bicarbonate (buffer) and enzymes for digestion (trypsinogen, lipase, etc.)

- endocrine - secretes products into blood: glucagons, insulin, and  somatostatin

Chemical Digestion –hydrolysis of polymers into monomers for absorption

-most absorption takes place in the small intestine, most completed by the time the food reaches the ileum

Carbohydrates (CHO)

-ingest about 200-400 grams of CHO daily, ingested monosaccharides are immediately absorbed (only three are common in our diet: glucose, fructose and galactose)

-complex CHO that we can digest are the disaccharides: sucrose, lactose (milk sugar), maltose (grain sugar), and the polysaccharides: glycogen and starch

-indigestible polysaccharides are the fiber in our diet

Complex CHO digestion begins with salivary amylase which splits starch into oligosaccharides (2-8 linked glucose molecules); works best in slightly acidic conditions; inactivated by the pH of stomach

-digestion continues with pancreatic amylase, within in 10 minutes all starch converted into oligosaccharides in the small intestine (mostly, maltose); then brush border enzymes break the sugars into monosaccharides (these include dextrinase, glucoamylase for oligosaccharides, and maltase, sucrase and lactase)

-absorption is accomplished mostly by cotransport mechanisms found in the brush border of the small intestine

Proteins

-begins in the stomach when pepsinogen is converted into pepsin; pepsin cleaves proteins into polypeptides and free amino acids by cleaving the peptide bond between tyrosine and phenylalanine.  It works best in an acid pH.

-upon entering the duodenum, protein fragments mix with trypsin, chymotrypsin, carboxypeptidase which further cleave the larger fragments into small peptides and poly peptides.  

-finally, brush border enzymes (carboxypeptidase, aminopeptidase and dipeptidase) complete the break down into amino acids for absorption

-most absorption by cotransport proteins found in brush border

Lipids

-the small intestine is the only major site of digestion; since the pancreas is the largest producer of lipase

-dietary fat accumulates as large globule that is resistant to digestion due to its size; bile salts mix in to the fat globule and promote the formation of 1mm droplets thus forming a fat emulsion.  This allows the lipase greater access to the triglyceride molecules which breaks the triglyceride into 2 fatty acids and a monoglyceride.

-the breakdown products again associate with bile salts forming micelles which penetrate close to the intestinal epithelial cell membrane; the lipids then diffuse readily through the cell membrane; also nestled within the fatty core of the micelle are cholesterol and fat soluble vitamins which follow the lipids into the cell.  Absorption is mostly accomplished in ileum.

-The fatty acids and monoglycerides are re-synthesized back into triglycerides by sER.  They are then combined with cholesterol, phospholipids and a coat of proteins to form chylomicrons contined within secretory vesicles in the Golgi.

-The vesicles are secreted out the base of the cell and the chylomicron enters the lacteal of the villus.  Eventually enters the bloodstream where lipoprotein lipase found in endothelial cells break down the triglycerides for entry into tissue cells or into adipose for storage.

Nucleic Acids

-Pancreatic nucleases break the NA down to their nucleotide monomers; brush border enzymes break these down into pentoses, phosphate ions, and free bases for active absorption into the blood stream.

-most of the absorbed material first enters the liver where much of it is processed

Nutrition State of the Body

Therefore; the body has two states regarding nutrition: 

1. Absorptive State -the body is assimilating nutrients; lasts up to four hours after a meal

2. Post-absorptive (Fasting) State -occurs after a meal is fully digested and assimilated; the body is no longer receiving new nutrients

Absorptive:-body's main energy source is absorbed glucose

glucose fate -> used as energy source by almost all cells (esp. brain)

-> converted to glycogen (glycogenesis) in liver and skeletal muscle

-> converted to fat acids (liver) and fat (lipogenesis) in adipose

Summary of effects:

1. energy provided by absorbed glu

2. net uptake of glu by liver

3. excess CHO, protein, and fat -> stored as fat

4. net synthesis of protein 

5. dominated by insulin form pancreas B-cells

Post-absorptive (fasting) State: -body energy provided by reserves

1. glycogenolysis -breakdown of glycogen in liver; releasing glu to blood

2. gluconeogenesis (liver) -creation of glucose from alternate sources

a. lactate and pyruvate released from skeletal muscle which liver converts to glu

b. protein catabolism from muscles and other cells -constitutes a

  major source of glucose in moderate fasts

c. glycerol liberated from fat catabolism

3. lipolysis -from adipose liberates glycerol and FA

-FA in blood used by all cells (except brain) through B-oxid

-liver can combine FA with Co-A to form ketone bodies (e.g. acetone)  which can be used by cells as E source (significant in prolonged fast because brain tissue can use these as alternate E source

-dominated by glucagon from A-cells.

Hormonal Regulation of Energy Metabolism:

Pancreas: endocrine and exocrine (islets a-insulin b-glucagon d-SS f-PP)

Insulin: (second messenger unknown -binds to memb. recp. and internalized)

secretion stimulated by: Increase glu in blood (major); Increase AA in blood;  Increase GI hormone levels; Increase Parasympathetic stimulation 

inhibited by:  Increase sympathetic stimulation; decrease glu in blood (major; self-regulating); by somatostatin from delta cells 

effects:

CHO

-increase uptake by all cells except brain and liver by action on glu membrane transport (increases insertion of glu transporter proteins in membrane)

-stimulates glycolysis 

-increases glycogenesis (net uptake of glu by liver)

-decreases glycogenolysis; decreases gluconeogenesis

-> net effect is to increase glu uptake and utilization and therefore decrease plasma glu   

LIPIDS

-increase lipogenesis; inhibits lipolysis; decreases ketogenesis

-increase FA transport into cell

--> net decrease in FA in plasma; Increase fat storage; decreases fat usage for energy

PROTEINS

-increase AA uptake; increase protein synthesis; inhibits catabolism

--> net decrease in plasma AA and net protein anabolism

Glucagon:

secretion stimulated by: decrease plasma glu; increase plasma AA;

      increase sympathetic or epinephrine 

      inhibited by:   increase plasma glu; parasympathetic stimulation

      SS and insulin secretion (perhaps PP)

effects: (uses cAMP as second messenger kinase phosphorylation); increases lipolysis, 

glycogenolysis, gluconeogenesis and ketone production;  net increase in liver glu secretion

 net increase in plasma glu (and FA (through hormone-sensitive lipase activation), glycerol, and ketones)

 (adrenalin has similar effects and may substitute if glucagon secretion deficient)

Exercise -similar to fast conditions but protein sparing in muscle

Diabetes Mellitus (due to hyposecretion of insulin or insulin resistance)

Type I (juvenile onset) insulin dependent results from loss of B-cells

 -may be autoimmune disease from several viral infections

 -less common form <10%

 -characterized by high levels of glu in blood but little to no insulin

therefore the cells cannot uptake glu efficiently and are starving in the midst of plenty

-polyphagia, polyuria (triggered by glu increase), polydipsia, glycouria, keturia

-FFA converted to ketones by liver and released in excess to body needs

-net result is metabolic acidosis

also protein catabolism increase due to lack of AA transport into cells leads to tissue depletion and growth failure and may contribute to decreased resistance to infections

Type II (mature onset) insulin independent (insulin resistance)

insulin present at above normal levels but receptors have decreased in number due to chronic down-regulation or Antibody attack which inhibits insulin binding

-may be associated with obesity which triggers chronic down regulation caloric restriction usually corrects this  (90% of diabetics)

-in addition , the chronic over production of the islets may result in hypertrophy and exhaustion of the B-cells which may lead to insulin dependency