HomeostasisHomeostasis – (maintaining a “steady state”) maintenance of

the conditions of the tissue fluid bathing the cells at a relatively constant level (pH, temperature, salt concentration)

• usually achieved by negative feedback – a change in the level of an internal factor causes effectors to restore the internal environment to its original level– an increase in body temperature causes the body to

lose more heat and vice versa• occasionally positive feedback is used such as in childbirth

– oxytocin is released, contractions occur, stimulate more release of oxytocin and therefore more contractions etc.

• ability of mammals to maintain a stable internal environment makes them independent of changing external conditions and enables them to exploit a wide range of habitats – ex. maintenance of internal body temperature

Control of Blood Glucose ConcentrationsGlucose is transported in solution in the blood

plasma• maintenance of glucose at steady levels is

vital• normal blood glucose concentration is about

90 - 100 mg of glucose per 100 cm3 of blood• Two interacting mechanisms control blood

glucose concentrations– insulin – compensates for glucose levels that are

too high– glucagon – compensates for glucose levels that

are too low

Insulin • small protein consisting of 51 amino acids• secreted by special cells called beta cells in the islets of

Langerhans which are special endocrine tissue in the pancreas

• when blood glucose concentrations rise above the set point, more insulin is secreted by the pancreas which results in:– an increase in the uptake of glucose and amino acids

into cells– an increase in the rate of cellular respiration and the use

of glucose as a respiratory substrate– an increase in the rate of conversion of glucose to fat in

adipose cells– an increase in the rate of conversion of glucose to

glycogen in liver and muscle cells (glycogenesis)

Glucagon • secreted by the alpha cells in the islets of

Langerhans• when blood glucose concentrations fall below set

point, the alpha cells secrete glucagons• glucagon activates phosphorylase (enzyme in

liver) which catalyzes the breakdown of glycogen to glucose (glycogenolysis)

• also increases the conversion of amino acids and glycerol into glucose 6-phosphate (to enter cellular respiration pathways)

• READ ABOUT DIABETES IN TEXTBOOK

The Liver• The liver is the largest organ in the human

abdomen – plays a central role in metabolism, regulating the levels of a wide range of chemicals in the blood and preventing harmful substances from reaching chemically sensitive organs such as the brain

Liver has a double blood supply – circulation:• hepatic artery – delivers oxygenated blood so that

liver cells can generate energy by aerobic respiration to carry out all their energy demanding functions

• hepatic portal vein – takes all the blood from the intestines (carrying all digested food, sugars, and amino acids) to the liver (blood vessel with the highest sugar concentration in body)

• enables liver to process substances absorbed from the digestive system before they enter general circulation – ex. poisons can be made harmless by detoxification before they damage brain

• hepatic vein – takes blood from the liver to the heart by merging into the inferior vena cava (blood vessel with highest concentration of urea)

• lymphatic vessels from the digestive system carry fatty substances to liver for processing before they go to rest of body (remember, fats are absorbed from the small intestine into the lymphatic system rather than into the blood)

Internal structure of the liverMade of numerous structures called lobules

• each lobule is made of a central vein in the center and tiny blood spaces called sinusoids radiating from it

• hepatic (liver) cells line up on both sides of the sinusoids

• hepatic cells have tiny canals between them called bile canaliculi – bile made by the hepatic cells trickle into these canaliculi and drain out into the bile duct

Process of bile production: • Bile is a yellow-green fluid containing water, bile

salts (derivatives of cholesterol that help to emulsify fats), bile pigments (products of the breakdown of hemoglobin, become yellow pigments in intestine, have no function but add to color of feces), inorganic salts, cholesterol and bicarbonate ions (HCO3

-) (to neutralize acid from stomach as food enters small intestine)

• bile is made by hepatic cells, travels via the bile canaliculi to the bile duct which empties into the gall bladder

• bile is stored in gall bladder

• blood from the hepatic portal vein and the hepatic artery pour blood into the sinusoids past each hepatic cell

• many chemical reactions are carried out by the liver in these cells

• sinusoids collect waste and CO2 from hepatic cells and all of the blood is sent to hepatic vein to leave the liver

The liver carries out many chemical processing functions:

• storage of minerals (including iron) and vitamins A (also called retinol – fat soluble), vitamin D (also called calciferol – fat soluble), and B12

– storage of iron – iron is a component of hemoglobin– liver stores iron left from the breakdown of old red blood

cells – this iron will be used again to produce new hemoglobin

• manufacture of plasma proteins (such as albumins) and blood clotting agents (including fibrinogen)

• detoxification of poisons – liver has a group of enzymes which break down chemicals into less harmful products (ex. catalase breaks hydrogen peroxide into water and oxygen)

The liver also has major roles in the metabolism of carbohydrates, fat, and protein as well as breaking down old red blood cells:

1. Carbohydrate metabolism – the liver helps to regulate blood glucose levels

– glucose concentration of blood leaving liver may be kept the same, reduced, or increased as compared to the blood that entered through the actions of glycogenolysis (converting glycogen to glucose), gluconeogenesis (converting amino acids or glycerol into glucose), or glycogenesis (storing glucose as glycogen) under influence of insulin and glucagon

2. Protein metabolism – regulation of amino acids and proteins

• the body cannot store excess proteins or amino acids• non-nitrogenous parts of amino acids can be converted to

fats or molecules that can enter Krebs cycle• nitrogen in amino group has to be eliminated from body

because it forms toxic substances• amino acids are first deaminated – removal of amino group

from amino acid to form ammonia• ammonia is very toxic and very soluble – terrestrial animals

convert it to a less toxic and less soluble substance to avoid harmful effects and to conserve water - urea

• liver deaminates amino acid forming ammonia• ammonia is immediately converted to urea in liver by

combining with carbon dioxide (process is actually a series of enzyme-catalyzed reactions called the ornithine cycle or urea cycle)

• urea is dumped into hepatic vein and leaves liver

Breakdown of old red blood cells in the liver• the liver is responsible for destruction and removal of old red

blood cells (erythrocytes)• old RBCs are eaten up by phagocytic cells of liver called

Kupffer cells – present in lining of sinusoids• the heme part of hemoglobin is broken down to a green

pigment called biliverdin• Biliverdin is broken into the yellow-brown pigment called

bilirubin• bilirubin is mixed with the bile and it becomes one of the

component of bile salts• bilirubin comes out with the feces and gives it a brown color• globin part of hemoglobin is digested into amino acids by

liver – recycled and used again to make proteins• iron from hemoglobin is stored in liver and is used for making

new hemoglobin

Temperature Control (Thermoregulation)

Humans are considered homeotherms (maintain a constant body temperature and are endotherms - regulate body temperature from within by heat produced by aerobic cellular respiration)

• body temperature is usually around 37o C – optimum temperature for enzyme activity

• body needs to maintain temperature regardless of changes in environmental temperatures

heat is lost to the environment by:

• conduction (transfer of heat between two objects in contact)

• radiation (release of heat in the form of waves from hot or warm objects – you radiate heat to surroundings)

• and convection (transfer of heat by convection currents in liquids and gases – you heat the air around you, it rises, and cold air sinks and replaces it)

Heat regulation in humans involves coordination between nervous and hormonal systems:

• thermoreceptors (nerve cells belonging to nervous system) under skin sense the change in surrounding environment

• thermoreceptors send nerve messages to hypothalamus (link between nervous and endocrine systems)

• hypothalamus releases TRH (thyroid releasing hormone) that travels to pituitary gland which then releases TSH (thyroid stimulating hormone) that travels to thyroid gland causing it to release the hormone, thyroxine

• thyroxine increases the metabolic rate of body releasing more heat – in hot weather, less thyroxine is released and less heat is generated

• hypothalamus also sends nerve messages to sweat glands, muscles, and blood capillaries in order to produce other responses such as sweating, shivering, vasoconstriction, and vasodilation

• heat regulation involves negative feedback – as temperature goes up, hypothalamus produces less TRH, pituitary releases less TSH, thyroid releases less thyroxine and metabolism reduces, reduced heat production and vice versa

Body temperature responses in cold weather:• thermoreceptors under skin sense decrease in

temp and send messages to hypothalamus in brain• hypothalamus also has thermoreceptors to sense

temp of blood• hypothalamus sends messages to different parts of

the body to cause the following changes:– vasoconstriction of blood vessels under the skin – less

blood near surface of skin reducing heat lost to atmosphere

– metabolic rate increases and more heat is generated– involuntary shivering causes release of heat by muscles– body hairs rise attempting to trap a layer of air between

them – trapped air is warmed by body and creates an insulating layer

Body temperature responses to hot weather:• thermoreceptors under skin send messages

to hypothalamus in brain causes the following responses:– vasodilation increases flow of blood under skin

so more heat is lost to atmosphere– sweating increases - when sweat evaporates it

takes heat from body surface resulting in cooling

– metabolic rate decreases and less heat is generated

– body hairs lay flat so they do not trap a layer of air between them

Gas Exchange• Gas exchange takes place at the alveoli

• Composition of alveolar air:

– gas in alveoli does not have same composition as atmospheric air

– each breath brings in fresh air that mixes with residual air

Composition of inspired (atmospheric air), alveolar, and expired air (percentage

composition by volume)Gas Inspired air alveolar air

expired airOxygen 20.95 13.8 16.4CO2 0.04 5.5 4.0

Nitrogen 79.01 80.7 79.6

• Blood arriving in lungs has a relatively high concentration of carbon dioxide and relatively low concentration of oxygen

– both gases diffuse down their concentration gradients to equalize between blood and air

Partial gas pressures

• partial pressure is usually used to compare the proportion of gases in a mixture

• the partial pressure of a gas in a mixture of gases is the pressure exerted by that gas (measured in kilopascals, kPa)

• ex. at sea level, total atmospheric pressure is 101.3 kPa

• atmosphere contains 21% oxygen, therefore oxygen has a partial pressure of

.21 x 101.3 kPa or 21.3 kPa

Hemoglobin and the transport of oxygen

• oxygen enters blood from alveoli and diffuses into red blood cells

• oxygen then combines with hemoglobin to form oxyhemoglobin (HbO2)

• as hemoglobin picks up the first molecule of oxygen, it increases its affinity for oxygen and picks up the next molecule even faster, the third and fourth are picked up even faster

• the degree of oxygenation of hemoglobin is determined by the partial pressure of oxygen (p(O2)) in the immediate surroundings

• If p(O2) is low (as in the capillaries at the tissues needing oxygen) hemoglobin releases oxygen and carries relatively small amounts of oxygen

• If p(O2) is high (such as at the alveoli) hemoglobin becomes almost saturated with oxygen

• an oxygen dissociation curve shows the degree of hemoglobin saturation with oxygen plotted against different values of p(O2) – the curve is S-shaped

• at p(O2) close to zero there is no oxygen bound to the hemoglobin

• at low p(O2), the polypeptide chains are tightly bound together, making it difficult for an oxygen molecule to attach to iron in heme group

• as one molecule of oxygen attaches, the polypeptide chain opens up exposing the other heme groups to oxygen and allowing oxygen to attach – the curves rises sharply

• at very high p(O2), the hemoglobin becomes saturated and the curve levels off

• oxygen at the muscles is taken over and stored by myoglobin

– myoglobin has a much higher affinity for oxygen than hemoglobin

– it binds with oxygen at a high rate and does not dissociate its oxygen unless the p(O2) drops to very low levels

– myoglobin stores oxygen in muscles until the demand becomes very great – during heavy exercise, muscles will get oxygen from hemoglobin first, then when supply oxygen from hemoglobin is exhausted, myoglobin will begin to release its oxygen

• Fetal (Foetal) hemoglobin– mother and child have separate circulatory

systems– fetus must be able to take oxygen from

mother’s hemoglobin in placenta– fetal hemoglobin is structurally different from

maternal hemoglobin (slightly different) – has a slightly higher affinity for oxygen than adult hemoglobin – oxygen released by maternal hemoglobin is bonded to fetal hemoglobin

Transport of carbon dioxideCarried from tissues to lungs in different ways:• most of the CO2 enters the red blood cells

and reacts with water to form carbonic acid (H2CO3) (catalyzed by the enzyme, carbonic anhydrase) – H2CO3 splits into H+ and bicarbonate ions (HCO3

-)• the bicarbonate ions leave the red blood

cells and are transported in the plasma• Chloride ions (Cl-) diffuse inwards from the

plasma to maintain electrical neutrality – this process is called the chloride shift

• Protons (H+) left inside the cell are taken up by the hemoglobin to form hemoglobinic acid (HHb) – this process causes the hemoglobin to release its oxygen

• therefore, higher CO2 causes hemoglobin to lose its affinity for oxygen – causes the Bohr shift

• higher CO2 levels cause the oxygen dissociation curve to shift to the right

• excess protons would cause acidity of blood to increase (lower pH) – hemoglobin acts as a buffer by taking up excess protons and preventing blood from becoming too acidic

Gas exchange at high altitudes • pressure is less at high altitudes therefore partial

pressure of oxygen is also less• mountain sickness may occur – fatigue, nausea,

breathlessness, headaches• body begins to acclimatize by:

– producing more RBCs – results in more hemoglobin to bind with oxygen

– breathing rate and depth increases by autonomic control from breathing center in brain stem

• People who live at high altitude have bigger lungs, larger vital capacity, and hemoglobin with an increased affinity for oxygen