human physiology.docx

8/14/2019 Human Physiology.docx

1/34

Human PhysiologyHepatic portal system

Inhuman anatomy,the hepatic portal systemis the system ofveins comprised ofthehepatic portal vein and its tributaries. It is also called the portal venous system,although it is not the only example of aportal venous system,and splanchnic veins, which

is notsynonymous with hepatic portal systemand is imprecise (as it

meansvisceral veinsand not necessarily the veins of theabdominal viscera).

Function

The portal venous system is responsible for directing blood from parts of thegastrointestinal

tract to theliver.Substances absorbed in the small intestine travel first to the liver forprocessing before continuing to the heart. Not all of thegastrointestinal tract is part of thissystem. The system extends from about the lower portion of theesophagus to the upper

part of theanal canal.It also includes venous drainage from thespleen andpancreas.Many drugs that are absorbed through theGI tract are substantially metabolized by theliver before reaching general circulation. This is known as thefirst pass effect.As a

consequence, certain drugs can only be taken via certain routes. For

example,nitroglycerin cannot be swallowed because the liver would inactivate themedication, but it can be takenunder the tongue or transdermal (through the skin) andthus is absorbed in a way that bypasses the portal venous system.

Blood flow to the liver is unique in that it receives both oxygenated and deoxygenatedblood. As a result, the partial pressure of oxygen (pO2) and perfusion pressure of portalblood are lower than in other organs of the body. Blood passes from branches of the portal

vein through cavities between "plates" ofhepatocytes calledsinusoids.Blood also flows

from branches of thehepatic artery and mixes in the sinusoids to supply the hepatocytes

with oxygen. This mixturepercolates through the sinusoids and collects in a central veinwhich drains into thehepatic vein.The hepatic vein subsequently drains into theinferior

vena cava.Large veins that are considered part of theportal venous systemare the:Hepatic portal vein

Splenic vein

Roughly, the portal venous system corresponds to areas supplied by theceliac trunk,thesuperior mesenteric artery,and theinferior mesenteric artery.
http://www.cssforum.com.pk/wiki/Human_anatomyhttp://www.cssforum.com.pk/wiki/Veinhttp://www.cssforum.com.pk/wiki/Hepatic_portal_veinhttp://www.cssforum.com.pk/wiki/Portal_venous_systemhttp://www.cssforum.com.pk/wiki/Synonymoushttp://www.cssforum.com.pk/wiki/Viscerahttp://www.cssforum.com.pk/wiki/Viscerahttp://www.cssforum.com.pk/wiki/Abdominalhttp://www.cssforum.com.pk/wiki/Gastrointestinal_tracthttp://www.cssforum.com.pk/wiki/Gastrointestinal_tracthttp://www.cssforum.com.pk/wiki/Liverhttp://www.cssforum.com.pk/wiki/Gastrointestinal_tracthttp://www.cssforum.com.pk/wiki/Esophagushttp://www.cssforum.com.pk/wiki/Anal_canalhttp://www.cssforum.com.pk/wiki/Spleenhttp://www.cssforum.com.pk/wiki/Pancreashttp://www.cssforum.com.pk/wiki/GI_tracthttp://www.cssforum.com.pk/wiki/First_pass_effecthttp://www.cssforum.com.pk/wiki/Nitroglycerinhttp://www.cssforum.com.pk/wiki/Sublingualhttp://www.cssforum.com.pk/wiki/Hepatocyteshttp://www.cssforum.com.pk/wiki/Liver_sinusoidhttp://www.cssforum.com.pk/wiki/Hepatic_arteryhttp://www.cssforum.com.pk/wiki/Percolationhttp://www.cssforum.com.pk/wiki/Hepatic_veinhttp://www.cssforum.com.pk/wiki/Inferior_vena_cavahttp://www.cssforum.com.pk/wiki/Inferior_vena_cavahttp://www.cssforum.com.pk/wiki/Inferior_vena_cavahttp://www.cssforum.com.pk/wiki/Hepatic_portal_veinhttp://www.cssforum.com.pk/wiki/Splenic_veinhttp://www.cssforum.com.pk/wiki/Celiac_trunkhttp://www.cssforum.com.pk/wiki/Superior_mesenteric_arteryhttp://www.cssforum.com.pk/wiki/Inferior_mesenteric_arteryhttp://www.cssforum.com.pk/wiki/Inferior_mesenteric_arteryhttp://www.cssforum.com.pk/wiki/Superior_mesenteric_arteryhttp://www.cssforum.com.pk/wiki/Celiac_trunkhttp://www.cssforum.com.pk/wiki/Splenic_veinhttp://www.cssforum.com.pk/wiki/Hepatic_portal_veinhttp://www.cssforum.com.pk/wiki/Inferior_vena_cavahttp://www.cssforum.com.pk/wiki/Inferior_vena_cavahttp://www.cssforum.com.pk/wiki/Hepatic_veinhttp://www.cssforum.com.pk/wiki/Percolationhttp://www.cssforum.com.pk/wiki/Hepatic_arteryhttp://www.cssforum.com.pk/wiki/Liver_sinusoidhttp://www.cssforum.com.pk/wiki/Hepatocyteshttp://www.cssforum.com.pk/wiki/Sublingualhttp://www.cssforum.com.pk/wiki/Nitroglycerinhttp://www.cssforum.com.pk/wiki/First_pass_effecthttp://www.cssforum.com.pk/wiki/GI_tracthttp://www.cssforum.com.pk/wiki/Pancreashttp://www.cssforum.com.pk/wiki/Spleenhttp://www.cssforum.com.pk/wiki/Anal_canalhttp://www.cssforum.com.pk/wiki/Esophagushttp://www.cssforum.com.pk/wiki/Gastrointestinal_tracthttp://www.cssforum.com.pk/wiki/Liverhttp://www.cssforum.com.pk/wiki/Gastrointestinal_tracthttp://www.cssforum.com.pk/wiki/Gastrointestinal_tracthttp://www.cssforum.com.pk/wiki/Abdominalhttp://www.cssforum.com.pk/wiki/Viscerahttp://www.cssforum.com.pk/wiki/Synonymoushttp://www.cssforum.com.pk/wiki/Portal_venous_systemhttp://www.cssforum.com.pk/wiki/Hepatic_portal_veinhttp://www.cssforum.com.pk/wiki/Veinhttp://www.cssforum.com.pk/wiki/Human_anatomy


2/34


3/34


4/34

The hepatic portal system begins in the capillaries of the digestive organs and ends in the

portal vein. Consequently, portal blood contains substances absorbed by the stomach and

intestines. Portal blood is passed through the hepatic lobules where nutrients and toxins are

absorbed, excreted or converted.

Restriction of outflow through the hepatic portal system can lead to portal hypertension.

Portal hypertension is most often associated with cirrhosis. Patients usually present with

splenomegaly, ascites, GI bleeding and/or portal systemic encephalopathy.

The consequences of portal hypertension are due to portal systemic anastomosis formed by

the body as an attempt to bypass the obstructed liver circulation. These collateral vessels

form along the falciform ligament, diaphragm, spleen, stomach and peritoneum. The

collaterals find their way to the renal vein where blood drained from the digestive organs is

let into the systemic circulation.

Blood Components

Normally, 7-8% of human body weight is from blood. In adults, this amounts


5/34

to 4-5 quarts of blood. This essential fluid carries out the critical functions of

transporting oxygen and nutrients to our cells and getting rid of carbondioxide, ammonia, and other waste products. In addition, it plays a vital role

in our immune system and in maintaining a relatively constant bodytemperature. Blood is a highly specialized tissue composed of many different

kinds of components. Four of the most important ones are red cells, whitecells, platelets, and plasma. All humans produce these blood components--

there are no populational or regional differences.

Red Cells

Red cells, or erythrocytes

, are relatively large microscopic cells without nuclei. In this latter trait, they are similar tothe primitiveprokaryotic cellsof bacteria. Red cells normally make up 40-50% of the total

blood volume. They transport oxygen from the lungs to all of the living tissues of the bodyand carry away carbon dioxide. The red cells are produced continuously in our bone marrow

fromstem cellsat a rate of about 2-3 million cells per second. Hemoglobinis the gas transportingproteinmolecule that makes up 95% of a red cell. Each red cell hasabout 270,000,000 iron-rich hemoglobin molecules. People who are anemic generally have

a deficiency in red cells. The red color of blood is primarily due to oxygenated red cells.Human fetal hemoglobin molecules differ from those produced by adults in the number ofamino acid chains. Fetal hemoglobin has three chains, while adults produce only two. As aconsequence, fetal hemoglobin molecules attract and transport relatively more oxygen to
http://www.cssforum.com.pk/glossary.htm/lprokaryotichttp://www.cssforum.com.pk/glossary.htm/lprokaryotichttp://www.cssforum.com.pk/glossary.htm/lprokaryotichttp://www.cssforum.com.pk/glossary.htm/lstem_cellshttp://www.cssforum.com.pk/glossary.htm/lstem_cellshttp://www.cssforum.com.pk/glossary.htm/lproteinshttp://www.cssforum.com.pk/glossary.htm/lproteinshttp://www.cssforum.com.pk/glossary.htm/lproteinshttp://www.cssforum.com.pk/glossary.htm/lproteinshttp://www.cssforum.com.pk/glossary.htm/lstem_cellshttp://www.cssforum.com.pk/glossary.htm/lprokaryotic


6/34

the cells of the body.

White Cells

White cells, or leukocytes

, exist in variable numbers and types but make up a very small part of blood's volume--normally only about 1% in healthy people. Leukocytes are not limited to blood. They occur

elsewhere in the body as well, most notably in the spleen, liver, and lymph glands. Most areproduced in our bone marrow from the same kind of stem cells that produce red blood cells.

Others are produced in the thymus gland, which is at the base of the neck. Some white cells(called lymphocytes

) are the first responders for our immune system. They seek out, identify, and bind to alien

protein onbacteria,viruses,andfungiso that they can be removed. Other white cells

(called granulocytesand macrophages) then arrive to surround and destroy the alien cells. They also have the function of getting

rid of dead or dying blood cells as well as foreign matter such as dust and asbestos. Red

cells remain viable for only about 4 months before they are removed from the blood andtheir components recycled in the spleen. Individual white cells usually only last 18-36 hoursbefore they also are removed, though some types live as much as a year. The description of

white cells presented here is a simplification. There are actually many specialized sub-types

of them that participate in different ways in our immune responses.
http://www.cssforum.com.pk/glossary.htm/lbacteriahttp://www.cssforum.com.pk/glossary.htm/lbacteriahttp://www.cssforum.com.pk/glossary.htm/lbacteriahttp://www.cssforum.com.pk/glossary.htm/lvirushttp://www.cssforum.com.pk/glossary.htm/lvirushttp://www.cssforum.com.pk/glossary.htm/lvirushttp://www.cssforum.com.pk/glossary.htm/lfungihttp://www.cssforum.com.pk/glossary.htm/lfungihttp://www.cssforum.com.pk/glossary.htm/lfungihttp://www.cssforum.com.pk/glossary.htm/lfungihttp://www.cssforum.com.pk/glossary.htm/lvirushttp://www.cssforum.com.pk/glossary.htm/lbacteria


7/34

Platelets

Platelets, or thrombocytes

, are cell fragments without nuclei that work with blood clotting chemicals at the site ofwounds. They do this by adhering to the walls of blood vessels, thereby plugging the

rupture in thevascularwall. They also can release coagulating chemicals which cause clots

to form in the blood that can plug up narrowed blood vessels. There are more than a dozen

types of blood clotting factors and platelets that need to interact in the blood clottingprocess. Recent research has shown that platelets help fight infections by releasing proteins

that kill invading bacteria and some other microorganisms. In addition, platelets stimulatethe immune system. Individual platelets are about 1/3 the size of red cells. They have alifespan of 9-10 days. Like the red and white blood cells, platelets are produced in bone

marrow from stem cells.
http://www.cssforum.com.pk/glossary.htm/lvascularhttp://www.cssforum.com.pk/glossary.htm/lvascularhttp://www.cssforum.com.pk/glossary.htm/lvascular


8/34

Plasma

Plasma

is the relatively clear liquid water (92+%), sugar, fat, protein and salt solution which carries

the red cells, white cells, platelets, and some other chemicals. Normally, 55% of our blood's

volume is made up of plasma. About 95% of it consists of water. As the heart pumps blood

to cells throughout the body, plasma brings nourishment to them and removes the waste

products ofmetabolism.Plasma also contains blood clotting factors, sugars,lipids,vitamins,

minerals,hormones,enzymes,antibodies,and otherproteins.It is likely that plasmacontains some of every protein produced by the body--approximately 500 have been

identified in human plasma so far.

Kidney Filteration

How does the mammalian kidney produce urine?

The kidney contains numerous functional units, called nephrons, which produce urine through a series of

steps: glomerular filtration of the blood, tubular reabsorption of the glomerular filtrate, and tubular

secretion of harmful substances.

Glomerular Filtration

Blood flows from the afferent arteriole into the glomerulus, a tuft of fenestrated capillaries enclosed in the

Bowmans capsule. Here 15 to 25 percent of the plasmas water and solutes are filtered through a single -

cell layer of the capillary walls, through a basement membrane, and into the lumen of the Bowmans

capsule. The filtrate then flows into the renal tubule, to undergo tubular reabsorption.

The rate of glomerular filtration depends on three factors: the hydrostatic pressure difference between the

capillaries and the Bowmans capsule (due to blood pressure), the colloid osmotic pressure, which

opposes filtration, and the hydraulic permeability of the three-layered tissue separating the capillaries and

the lumen of the Bowmans capsule. Overall, blood pressure in the body has a major effect on the

glomerular filtration rate, because the amount of blood passing through the glomerulus determines how

much and how fast the fluid can be filtered. Among the dangers of very low blood pressure, therefore, is

the loss of kidney function. This is a primary reason for the use of inflatable "shock suits" on the lower

body in cases of extreme blood loss from trauma. By reducing blood flow to the legs, blood pressure in
http://www.cssforum.com.pk/glossary.htm/lmetabolismhttp://www.cssforum.com.pk/glossary.htm/lmetabolismhttp://www.cssforum.com.pk/glossary.htm/lmetabolismhttp://www.cssforum.com.pk/glossary.htm/llipidhttp://www.cssforum.com.pk/glossary.htm/llipidhttp://www.cssforum.com.pk/glossary.htm/llipidhttp://www.cssforum.com.pk/glossary.htm/lhormoneshttp://www.cssforum.com.pk/glossary.htm/lhormoneshttp://www.cssforum.com.pk/glossary.htm/lhormoneshttp://www.cssforum.com.pk/glossary.htm/lenzymehttp://www.cssforum.com.pk/glossary.htm/lenzymehttp://www.cssforum.com.pk/glossary.htm/lenzymehttp://www.cssforum.com.pk/glossary.htm/lantibodieshttp://www.cssforum.com.pk/glossary.htm/lantibodieshttp://www.cssforum.com.pk/glossary.htm/lantibodieshttp://www.cssforum.com.pk/glossary.htm/lproteinshttp://www.cssforum.com.pk/glossary.htm/lproteinshttp://www.cssforum.com.pk/glossary.htm/lproteinshttp://www.cssforum.com.pk/glossary.htm/lproteinshttp://www.cssforum.com.pk/glossary.htm/lantibodieshttp://www.cssforum.com.pk/glossary.htm/lenzymehttp://www.cssforum.com.pk/glossary.htm/lhormoneshttp://www.cssforum.com.pk/glossary.htm/llipidhttp://www.cssforum.com.pk/glossary.htm/lmetabolism


9/34

the trunk is kept higher, in an effort to maintain kidney function.

The body through endocrine responses can regulate the glomerular filtration rate. In the case of auto

regulation, increased blood pressure stretches walls of the afferent arteriole, which responds by

contracting - thereby reducing fluctuation of blood pressure in the glomerulus. A drop in blood pressure

brings about a decrease in the glomerular filtration rate, which, in turn, results in a decrease in sodium

ions in the filtrate. (The filtrate moves through the nephrons more slowly, allowing more sodium to be

reabsorbed along the way.). This lower sodium level in the filtrate is detected by the macula densa,

modified cells of the wall of the distal convoluted tubule that lie adjacent to the afferent and efferent

arterioles of the glomerulus. In response to the low sodium, cells of the juxtaglomerular apparatus (JGA)

release rennin. This triggers a series of biochemical reactions which bring about an increase of blood

pressure, and thereby an increase in GFR. This series of reactions includes an increase in angiotensin II,

which helps bring blood pressure back up by (1) causing vasoconstriction in arterioles throughout much of

the body, and (2) promoting increased synthesis of antidiiuretic hormone (ADH), which increases

resorption of water in the collecting ducts of the kidney, thereby increasing blood volume. Angiotensin II

also promotes the release of aldosterone from adrenal cortex, which promotes retention of both sodium

and water, thereby helping to bring blood pressure back up.The glomerular filtration rate can also be regulated by sympathetic nerve responses, which can result in

the constriction or dilation of the afferent arterioles in times of great bodily stress. Vasoconstriction

increases blood pressure, and therefore GFR, whereas vasodilation decreases blood pressure and GFR.

Tubular Reabsorption

As the glomerular filtrate moves through the nephron, it changes composition dramatically. About 99% of

the water in the original filtrate is reabsorbed, and less than 1% of the original NaCl content appears in

the final urine. How does this happen? First, the filtrate moves into the proximal tubule, where about 70%

of the sodium ions are reabsorbed through active transport. Water and chloride ions follow passively.

Glucose and amino acids are reabsorbed here. Approximately 75% of the glomerular filtrate is

reabsorbed in the proximal tubule. This is aided by the so-called "brush border" of microvilli cells which

function in increasing the surface area for reabsorption.

After moving through the proximal tubule, the filtrate moves on to the descending limb of the Loop of

Henle. The cells in this area have no brush border, and there is no active salt transport here. The cells

have a low permeability to urea and salt, but are very permeable to water. As the filtrate descends the

Loop of Henle, water diffuses out because of the high salt concentration in the surrounding tissue. This is

part of the urine-concentrating system of the nephron. The Loop of Henle acts as a countercurrent

multiplier. For this reason, mammals living in marine or desert environments have longer loops of Henle

and can conserve more water by producing more concentrated urine.

The filtrate moves along the Loop of Henle to the thin segment of the ascending limb, which is highly

permeable to Na+ and Cl-, and impermeable to water and urea. As the filtrate moves up the thin segment,

Na+ and Cl- diffuse out because there is a higher concentration in the filtrate than in the surrounding

tissues. The filtrate then moves to the medullary thick ascending limb, which is involved in the active

transport of Na+ and Cl- outward from the lumen into the interstitial space. This causes the fluid reaching

the distal tubule to be hypoosmotic to the interstitial fluid, and allows for the passive transport of water out


10/34

of the tubule.

The distal tubule functions in transporting K+, H+, and NH3 into the lumen, and Na+, Cl-, and HCO3- out.

Transport of salts in this area is under endocrine control and adjusted according to osmotic conditions.

The filtrate then moves into the collecting duct, which carries the fluid to the renal pelvis, to the ureters,

and out of the body through the urethra. The epithelium of the collecting duct is permeable to water, but

not salt or urea. The hormone ADH from the posterior pituitary gland controls the permeability o the

collecting duct to water. This response causes the filtrate, which is hypoosmotic to the interstitial fluid at

this point, to lose water by osmosis and therefore increase the concentration of salts and urea in the

urine. At the bottom of the collecting duct, the epithelium is permeable to urea. The diffusion of some urea

out of the filtrate and into the surrounding tissue helps produce the interstitial concentration gradient

necessary for the diffusion of water out of the descending limb of the Loop of Henle. The urea also helps

draw water out of the filtrate passing down the collecting duct, thereby enabling the kidney to excrete

urine that is hypertonic to the general body fluids, a property that is important in water conservation.

Tubular Secretion

In several places along the nephron, substances that are not part of the initial filtrate (because the

molecules are too big to be filtered through the glomerulus) are actively transported from the blood into

the filtrate for elimination from the body in the urine. Some substances, such as toxins and drugs, are

processed in the liver and conjugated with glucouronic acid. This marks them for removal from blood

capillaries in the kidney and transport into the lumen of the nephron to become part of the filtrate.

How do the kidneys regulate pH?

Regulation of pH is governed by the carbon dioxide/bicarbonate buffering system in the body, which

consists of three steps:

CO2 + H2O H2CO3 HCO3- + H+

CO2 + OH- + H+ HCO3- + H+

HOH OH- + H+

The excretion of acid by the kidney is one of the two major factors, which influence this system (the other

being the excretion of carbon dioxide by the lungs). The excretion of hydrogen ions (acid) in the urine is

primarily responsible for maintaining the plasma HCO3- concentration. Mammalian urine is mildly acidic,

with a pH of about 6, and contains no bicarbonate. However, the initial glomerular filtrate has a high

bicarbonate concentration and a low hydrogen ion concentration. Therefore, in the process of urine

formation, acid must be added to the filtrate, and bicarbonate must be removed. Therefore, the excretion

of H+ and the recovery of HCO3- are both important mechanisms by which the kidneys help the body

regulate pH.

Special cells in the distal tubule and collecting duct, called A-type cells and B-type cells, accomplish this


11/34

process. The A-type cells are acid-secreting cells that have a proton ATPase in the apical membrane and

a Cl-/ HCO3- exchange system in the basolateral membrane. The cells also contain carbonic anhydrase,

which hydrates carbon dioxide passing through the membrane to form protons and bicarbonate ions. The

protons formed are pumped back into the lumen and can react with the bicarbonate in the filtrate to form

carbon dioxide and water, which can diffuse back into the cell, and create an uptake of bicarbonate back

into the blood.

B-type cells, on the other hand, are base-secreting cells. They have a different form of

chloride/bicarbonate exchanger in the apical membrane than the A-type cells, and secrete bicarbonate

into the lumen of the tubule in exchange for chloride ions.

Regulation of pH is accomplished then, by altering the activity of A and B-type cells, which determines

whether bicarbonate is reabsorbed or secreted.

Another mechanism used in pH regulation is the uptake of H+ by HPO4- and NH3 in the lumen to trap

excess H+ in the filtrate. This occurs in order to bind H+ with something so that these protons will not

move back into the epithelial cells and the blood, which would lower pH.

Excretion and osmoregulation

The major problems that animals face with regard to osmoregulation

In most animals, the majority of cells are not in direct contact with the external environment but arebathed by an internal body fluid. Homeostatic mechanisms hamper changes in an animals body fluid,which both gives protection from harmful external environments and impedes quick exchange betweenintracellular compartments. The cells of the animal cannot survive much additional water gain or loss.Water continuously enters and leaves an animal cell across the plasma membrane, however, uptake andloss must balance. Animal cells swell and burst if there is a net uptake of water or shrivel and die it thereis a net loss of water.

Other problems associated with osmoregulation are body and environment temperatures. The enzymeactivity in the body function between temperatures of 0o40o Celsius. The way animals deal withtemperature and regulating it is by way of water loss. So animals in hot environments need to limit theamount of water loss due to evaporation and respiration. The importance of water in temperatureregulating leads to conflicts and compromises between physiological adaptations to environmentaltemperatures and osmotic stresses in terrestrial animals.

The major structures involved in osmoregulation and excretion

Organisms in different environments utilize different structures in osmoregulation and excretion. The

major structures involved are the integument, the respiratory surface, the kidney, and the salt gland. Allanimals use at least one of these structures in their osmoregulatory processes. The commoncharacteristic in structures such as gills, skin, kidneys and the integument are cells called transportepithelia, anatomically and functionally polarized cells which determine the osmoregulatory capabilities ofthe structure, through properties such as permeability to various solutes.

The integumentfunctions in osmoregulation by acting as a barrier between the extracellular compartmentand the environment to regulate water gain and loss, as well as solute flux. The permeablity of theintegument to water and solutes varies from animal to animal.


12/34

Respiratory surfaces such as the alveoli of the lung, and gills in aquatic animals also serve inosmoregulation and excretion. Respiratory surfaces are the chief avenues for the excretion of carbondioxide and metabolic water, as well as other gaseous wastes, in animals. The kidney is the main organ involved in maintaining water balance and excreting harmful substances inmammals.

Elasmobranchs, marine birds, and some reptiles have a structure called a salt glandto secrete NaCl fromtheir bodies. These animals require a lower internal NaCl concentration than the surrounding seawater,which causes a concentration gradient favoring the influx of salt. Therefore, they need a way to secrete it.The solution is provided by glands in the rectum of sharks and the skulls of marine birds and reptileswhich produces a concentrated salt solution for secretion. The sodium ions are removed from the bloodby these glands not by filtration, but by the sodium-transport mechanism (the sodium-potassium pump).This Na+/ K+ / ATPase activity allows for the movement of NaCl from the blood across the epithelium intothe lumen of the salt gland for secretion.

Interestingly, the shark rectal gland, bird nasal gland, fish gill, and the thick ascending Loop of Henle inthe kidney all contain salt-secreting cells that transport NaCl by the same basic mechanism. Activetransport produces an increase in the chloride concentration in the cytoplasm of epithelial cells. Thisresults in the diffusion of chloride ions out of the cell across the apical surface. The build-up of chlorideions at the apical surface attracts sodium ions to diffuse between the cells (the paracellular route).Insects have a network of Malpighian tubules extending throughout much of the body cavity and attachedto the alimentary canal between the midgut and the hindgut. The secretory cells which line the walls ofthese long, thin tubules secrete KCl, NaCl, and phosphate from the hemolymph (blood) into the lumen ofthe tubule. Smaller molecules, such as water, amino acids, and sugars diffuse down their concentrationgradient and into the lumen. The fluid then flows along the tubule and into the gut. As the fluid passesthrough the hindgut, water and valuable ions are transported back into the hemolymph, leaving behind aconcentrated waste for excretion from the body.

Why and how do organisms excrete metabolic wastes (particularly nitrogenous wastes)?

Waste products generated in metabolic processes are often toxic, and therefore must be eliminated

before they can harm the organism. The major metabolic wastes produced by animals include carbondioxide, metabolic water, and nitrogenous wastes. Small aquatic organisms are able to get rid of wastesby simple diffusion across membranes. More complex animals with circulatory systems rely on kidneys tofilter wastes out of the blood and eliminate them from the body.

Carbon dioxide and metabolic water produced in respiration easily diffuse into the environment fromrespiratory surfaces. Nitrogenous waste excretion is more difficult, yet necessary. Elevated ammonialevels in the body can lead to convulsions, coma, and even death. This is because ammonium ions cansubstitute for potassium ions in ion-exchange mechanisms. Ammonia can also adversely affectmetabolism and amino acid transport. An excessive amount of ammonia in the system elevates bodilypH, which causes changes in the tertiary structure of proteins, and thus cellular functions can be altered.There are three main types of nitrogenous wastes: ammonia, urea, and uric acid. The type of waste an

animal excretes depends on its living environment, because nitrogenous waste excretion is accompaniedby a certain amount of water loss. Ammonotelic (ammonia-excreting) animals generally live only inaquatic habitats, because ammonia is extremely toxic, and a large volume of water is required to maintainthe excreted ammonia level lower than the body level. This is needed because ammonia excretion relieson passive diffusion, so a gradient is required between the organism and the environment in order for theammonia to flow from high concentration to low concentration.Whereas most excretion of ammonia occurs across the gills of aquatic animals, mammals do excretesome ammonia in the urine. Amino groups are enzymatically transformed into glutamate, and thenchanged to glutamine in the liver. Glutamine can cross the kidney membranes (whereas amino acids can


13/34

not). In the kidney tubules, the glutamine is deaminated to ammonia and then excreted in the urine.

Although ammonia excretion is present in some forms in mammals, the major nitrogenous waste excretedis urea. Urea is less toxic than ammonia, and requires less water for elimination. Therefore, ureotelic(urea-excreting) animals are most often (but not exclusively) terrestrial. A downside to urea excretion is

that urea synthesis requires energy, in the form of ATP. Vertebrates synthesize urea in the liver using theornithine-urea cycle. Teleosts and invertebrates produce urea from uric acid via the uricolytic pathway.

Birds, reptiles, and most terrestrial arthropods often are subject to very limited water availability, so evenurea excretion is not possible. Therefore, these uricotelic (uric acid-excreting) animals synthesize uricacid, which requires even less water than urea for elimination. The ability to produce uric acid, which isrelatively insoluble, is quite important to birds and reptiles prior to hatching. Nitrogenous wastes can besafely stored within the egg in the form of uric acid, whereas a build-up of either ammonia or urea wouldbe deadly.

Human Vertebral System

In vertebrate animals, the flexible column extending from neck to tail, made of a series of bones,

the vertebrae. The major function of the vertebral column is protection of the spinal cord; it alsoprovides stiffening for the body and attachment for the pectoral and pelvic girdles and many

muscles. In humans an additional function is to transmitbody weight in walking and standing.

Eachvertebra,in higher vertebrates, consists of aventral body,or centrum, surmounted by a Y-shaped neural arch. The arch extends a spinous process (projection) downward and backward

that may be felt as a series of bumps down the back, and two transverse processes, one to either

side, which provide attachment for muscles and ligaments. Together the centrum and neural arch

surround an opening, the vertebral foramen, through which thespinal cordpasses. The centrumsare separated by cartilaginousintervertebral disks,which help cushion shock in locomotion.Vertebrae in lower vertebrates are more complex, and the relationships of their parts to those of

higher animals are often unclear. In primitive chordates (e.g.,amphioxus, lampreys) a rodlike

structure, thenotochord,stiffens the body and helps protect the overlying spinal cord. Thenotochord appears in the embryos of all vertebrates in the space later occupied by the vertebral

bodiesin some fish it remains throughout life, surrounded by spool-shaped centrums; in other

vertebrates it is lost in the developed animal. In primitive chordates the spinal cord is protecteddorsally by segmented cartilagesthese foreshadow the development of the neural arch of true

vertebrae.

Fish have trunk and caudal (tail) vertebrae; in land vertebrates with legs, the vertebral column

becomes further subdivided into regions in which the vertebrae have different shapes andfunctions. Crocodilians and lizards, birds, and mammals demonstrate five regions: (1)cervical,

in the neck, (2) thoracic, in the chest, which articulates with the ribs, (3) lumbar, in the lower

back, more robust than the other vertebrae, (4) sacral, often fused to form a sacrum, whicharticulates with thepelvic girdle,(5) caudal, in the tail. The atlas and axis vertebrae, the top two

cervicals, form a freely movable joint with the skull.

The numbers of vertebrae in each region and in total vary with the species. Snakes have thegreatest number, all very similar in type. Inturtles some vertebrae may be fused to the shell

(carapace); in birds all but the cervical vertebrae are usually fused into a rigid structure, which
http://www.britannica.com/EBchecked/topic/71189/body-weighthttp://www.britannica.com/EBchecked/topic/626576/vertebrahttp://www.britannica.com/EBchecked/topic/102920/centrumhttp://www.britannica.com/EBchecked/topic/560043/spinal-cordhttp://www.britannica.com/EBchecked/topic/291801/intervertebral-diskhttp://www.britannica.com/EBchecked/topic/420637/notochordhttp://www.britannica.com/EBchecked/topic/103707/cervical-vertebrahttp://www.britannica.com/EBchecked/topic/449463/pelvic-girdlehttp://www.britannica.com/EBchecked/topic/610454/turtlehttp://www.britannica.com/EBchecked/topic/610454/turtlehttp://www.britannica.com/EBchecked/topic/449463/pelvic-girdlehttp://www.britannica.com/EBchecked/topic/103707/cervical-vertebrahttp://www.britannica.com/EBchecked/topic/420637/notochordhttp://www.britannica.com/EBchecked/topic/291801/intervertebral-diskhttp://www.britannica.com/EBchecked/topic/560043/spinal-cordhttp://www.britannica.com/EBchecked/topic/102920/centrumhttp://www.britannica.com/EBchecked/topic/626576/vertebrahttp://www.britannica.com/EBchecked/topic/71189/body-weight


14/34

lends support in flight. Most mammals have seven cervical vertebrae; size rather than number

account for the variations in neck length in different species.Whales show several

specializationsthe cervical vertebrae may be either much reduced or much increased innumber, and the sacrum is missing. Humans have 7 cervical, 12 thoracic, 5 lumbar, 5 fused

sacral, and 3 to 5 fused caudal vertebrae (together called the coccyx).

The vertebral column is characterized by a variable number of curves. In quadrupeds the columnis curved in a single arc (the highest portion occurring at the middle of the back), whichfunctions somewhat like a bow spring in locomotion. In humans this primary curve is modified

by three more: (1) a sacral curve, in which the sacrum curves backward and helps support the

abdominal organs, (2) an anterior cervical curve, which develops soon after birth as the head israised, and (3) a lumbar curve, also anterior, which develops as the child sits and walks. The

lumbar curve is a permanent characteristic only of humans and their bipedal forebears, though a

temporary lumbar curve appears in other primates in the sitting position. The cervical curve

disappears in humans when the head is bent forward but appears in other animals as the head israised.

Human skeletal system

Thevertebral column is not actually a column but rather a sort of spiral spring in the form of theletter S. The newborn child has a relatively straight backbone. The development of the curvatures

occurs as the supporting functions of the vertebral column in humansi.e., holding up the trunk,

keeping the head erect, serving as an anchor for the extremitiesare developed.The S-curvature enables the vertebral column to absorb the shocks of walking on hard surfaces; a

straight column would conduct the jarring shocks directly from the pelvic girdle to the head. The

curvature meets the problem of the weight of the viscera. In an erect animal with a straight

column, the column would be pulled forward by the viscera. Additional space for the viscera isprovided by the concavities of the thoracic and pelvic regions.

Weight distribution of the entire body is also effected by the S-curvature. The upper sector to alarge extent carries the head; the central sector carries the thoracic viscera, the organs andstructures in the chest; and the lower sector carries the abdominal viscera. If the column were

straight, the weight load would increase from the head downward and be relatively great at the

base. Lastly, the S-curvature protects the vertebral column from breakage. The doubly bentspring arrangement is far less vulnerable to fracture than would be a straight column.The protective function of the skeleton is perhaps most conspicuous in relation to thecentral

nervous system,although it is equally important for the heart and lungs and some other organs. A

high degree of protection for thenervous system is made possible by the relatively small amountof motion and expansion needed by the component parts of this system and by certainphysiological adaptations relating to circulation, to thecerebrospinal fluid,and to themeninges,

the coverings of the brain and spinal cord. Thebrain itself is snugly enclosed within the boxlikecranium. Sharing in the protection afforded by the cranium is thepituitary gland,or hypophysis.

Inhuman anatomy,the vertebral column(backboneor spine) is a column usually consisting of

24vertebrae,[1] thesacrum,intervertebral discs,and thecoccyx situated in thedorsal aspect ofthetorso,separated byspinal discs.It houses thespinal cord in itsspinal canal.Curves
http://www.britannica.com/EBchecked/topic/641397/whalehttp://www.britannica.com/EBchecked/topic/626589/vertebral-columnhttp://www.britannica.com/EBchecked/topic/102504/central-nervous-systemhttp://www.britannica.com/EBchecked/topic/102504/central-nervous-systemhttp://www.britannica.com/EBchecked/topic/409709/human-nervous-systemhttp://www.britannica.com/EBchecked/topic/103430/cerebrospinal-fluidhttp://www.britannica.com/EBchecked/topic/375044/meningeshttp://www.britannica.com/EBchecked/topic/77269/brainhttp://www.britannica.com/EBchecked/topic/462264/pituitary-glandhttp://en.wikipedia.org/wiki/Human_anatomyhttp://en.wikipedia.org/wiki/Vertebrahttp://en.wikipedia.org/wiki/#cite_note-0http://en.wikipedia.org/wiki/Sacrumhttp://en.wikipedia.org/wiki/Intervertebral_dischttp://en.wikipedia.org/wiki/Coccyxhttp://en.wikipedia.org/wiki/Dorsum_(biology)http://en.wikipedia.org/wiki/Torsohttp://en.wikipedia.org/wiki/Spinal_dischttp://en.wikipedia.org/wiki/Spinal_cordhttp://en.wikipedia.org/wiki/Spinal_canalhttp://en.wikipedia.org/wiki/Spinal_canalhttp://en.wikipedia.org/wiki/Spinal_cordhttp://en.wikipedia.org/wiki/Spinal_dischttp://en.wikipedia.org/wiki/Torsohttp://en.wikipedia.org/wiki/Dorsum_(biology)http://en.wikipedia.org/wiki/Coccyxhttp://en.wikipedia.org/wiki/Intervertebral_dischttp://en.wikipedia.org/wiki/Sacrumhttp://en.wikipedia.org/wiki/#cite_note-0http://en.wikipedia.org/wiki/Vertebrahttp://en.wikipedia.org/wiki/Human_anatomyhttp://www.britannica.com/EBchecked/topic/462264/pituitary-glandhttp://www.britannica.com/EBchecked/topic/77269/brainhttp://www.britannica.com/EBchecked/topic/375044/meningeshttp://www.britannica.com/EBchecked/topic/103430/cerebrospinal-fluidhttp://www.britannica.com/EBchecked/topic/409709/human-nervous-systemhttp://www.britannica.com/EBchecked/topic/102504/central-nervous-systemhttp://www.britannica.com/EBchecked/topic/102504/central-nervous-systemhttp://www.britannica.com/EBchecked/topic/626589/vertebral-columnhttp://www.britannica.com/EBchecked/topic/641397/whale


15/34

Viewed laterally the vertebral column presents several curves, which correspond to the differentregions of the column, and are calledcervical,thoracic,lumbar,and pelvic.The cervical curve, convex forward, begins at the apex of the odontoid (tooth-like) process, and

ends at the middle of the second thoracic vertebra; it is the least marked of all the curves.The thoracic curve, concave forward, begins at the middle of the second and ends at the middle

of the twelfth thoracic vertebra. Its most prominent point behind corresponds to the spinous

process of the seventh thoracic vertebra. This curve is known as a tt curve.

The lumbar curve is more marked in thefemale than in themale;it begins at the middle of thelast thoracic vertebra, and ends at the sacrovertebral angle. It is convex anteriorly, the convexity

of the lower three vertebrae being much greater than that of the upper two. This curve is

described as a lordotic curve.The pelvic curve begins at the sacrovertebral articulation, and ends at the point of thecoccyx;its

concavity is directed downward and forward.The thoracic and pelvic curves are termed primary curves, because they alone are present

duringfetal life. The cervical and lumbar curves are compensatoryorsecondary, and aredeveloped afterbirth,the former when the child is able to hold up its head (at three or four

months) and to sit upright (at nine months), the latter at twelve or eighteen months, when the

child begins to walk.Names of individual vertebrae

Individual vertebrae named according to region and position, from superior to inferior

Cervical7 vertebrae (C1-C7)

o C1 is known as "atlas" and supports the head, C2 is known as "axis"

o Possesses bifid spinous processes, which is absent in C7o Small-bodied

Thoracic12 vertebrae (T1-T12)

o Distinguished by the presence of costal facets for the articulation of the heads ofribs

o Body is intermediate in size between the cervical and lumbar vertebrae

Lumbar5 vertebrae (L1-L5)

o Has a large bodyo Does not have costal facets nor transverse process foramina

Sacral5 (fused) vertebrae (S1-S5)

Coccygeal4 (3-5) (fused) vertebrae (Tailbone)
http://en.wikipedia.org/wiki/Cervical_vertebraehttp://en.wikipedia.org/wiki/Thoracic_vertebraehttp://en.wikipedia.org/wiki/Lumbar_vertebraehttp://en.wikipedia.org/wiki/Femalehttp://en.wikipedia.org/wiki/Malehttp://en.wikipedia.org/wiki/Coccyxhttp://en.wikipedia.org/wiki/Fetushttp://en.wikipedia.org/wiki/Childbirthhttp://en.wikipedia.org/wiki/Childbirthhttp://en.wikipedia.org/wiki/Fetushttp://en.wikipedia.org/wiki/Coccyxhttp://en.wikipedia.org/wiki/Malehttp://en.wikipedia.org/wiki/Femalehttp://en.wikipedia.org/wiki/Lumbar_vertebraehttp://en.wikipedia.org/wiki/Thoracic_vertebraehttp://en.wikipedia.org/wiki/Cervical_vertebrae


16/34


17/34

Gaseous Exchange

Breathing consists of two phases, inspiration and expiration. During inspiration, the

diaphragm and the intercostal muscles contract. The diaphragm moves downwardsincreasing the volume of the thoracic (chest) cavity, and the intercostal muscles pull the

ribs up expanding the rib cage and further increasing this volume. This increase of volume

lowers the air pressure in the alveoli to below atmospheric pressure. Because air alwaysflows from a region of high pressure to a region of lower pressure, it rushes in through therespiratory tract and into the alveoli. This is called negative pressure breathing, changing

the pressure inside the lungs relative to the pressure of the outside atmosphere. In contrast

to inspiration, during expiration the diaphragm and intercostal muscles relax. This returnsthe thoracic cavity to it's original volume, increasing the air pressure in the lungs, and


18/34

forcing the air out.

External Respiration

When a breath is taken, air passes in through the nostrils, through the nasal passages, intothe pharynx, through the larynx, down the trachea, into one of the main bronchi, then into

smaller broncial tubules, through even smaller bronchioles, and into a microscopic air saccalled an alveolus. It is here that external respiration occurs. Simply put, it is the exchange

of oxygen and carbon dioxide between the air and the blood in the lungs. Blood enters thelungs via the pulmonary arteries. It then proceeds through arterioles and into the alveolar

capillaries. Oxygen and carbon dioxide are exchanged between blood and the air. This blood

then flows out of the alveolar capillaries, through vaneuoles, and back to the heart via thepulmonary veins. For an explanation as to why gasses are exchanged here, see partial

pressure.

Gas Transport

If 100mL of plasma is exposed to an atmosphere with a pO2 of 100mm Hg, only 0.3mL of

oxygen would be absorbed. However, if 100mL of blood is exposed to the same

atmosphere, about 19mL of oxygen would be absorbed. This is due to the presence ofhemoglobin, the main means of oxygen transport in the body. The respiratory pigment

hemoglobin is made up of an iron-containing porphyron, haem, combined with the proteinglobin. Each iron atom in haem is attached to four pyrole groups by covalent bonds. A fifthcovalent bond of the iron is attached to the globin part of the molecule and the sixth

covalent bond is available for combination with oxygen. There are four iron atoms in each

heamoglobin molecule and therefore four heam groups.

Oxygen Transport

In the loading and unloading of oxygen, there is a cooperation between these four haemgroups. When oxygen binds to one of the groups, the others change shape slighty and their

attraction to oxygen increases. The loading of the first oxygen, results in the rapid loadingof the next three (forming oxyhaemoglobin). At the other end, when one group unloads it'soxygen, the other three rapidly unload as their groups change shape again having lessattraction for oxygen. This method of cooperative binding and release can be seen in the

dissociation curve for hemoglobin. Over the range of oxygen concentrations where the curvehas a steep slope, the slightest change in concentration will cause hemoglobin to load orunload a substantial amount of oxygen. Notice that the steep part of the curve corresponds

to the range of oxygen concentrations found in the tissues. When the cells in a particular

location begin to work harder, e.g. during exercise, oxygen concentration dips in thatlocation, as the oxygen is used in cellular respiration. Because of the cooperation betweenthe haem groups, this slight change in concentration is enough to cause a large increase in

the amount of oxygen unloaded.

As with all proteins, hemoglobins shape shift is sensitive to a variety of environmentalconditions. A drop in pH lowers the attraction of hemoglobin to oxygen, an effect known as

the Bohr shift. Because carbon dioxide reacts with water to produce carbonic acid, an activetissue will lower the pH of it's surroundings and encourage hemoglobin to give up extra

oxygen, to be used in cellular respiration. Hemoglobin a notable molecule for it's ability to

transport oxygens from regions of supply to regions of demand.Carbon Dioxide Transport- Out of the carbon dioxide released from respiring cells, 7%dissolves into the plasma, 23% binds to the multiple amino groups of hemoglobin

(Caroxyhaemoglobin), and 70% is carried as bicarbonate ions. Carbon dioxide created by


19/34

respiring cells diffuses into the blood plasma and then into the red blood cells, where most

of it is converted to bicarbonate ions. It first reacts with water forming carbonic acid, which

then breaks down into H+ and CO3-. Most of the hydrogen ions that are produced attach tohemoglobin or other proteins. In thisInternal RespirationThe body tissues need the oxygen and have to get rid of the carbon dioxide, so the blood

carried throughout the body exchanges oxygen and carbon dioxide with the body's tissues.Internal respiration is basically the exchange of gasses between the blood in the capillaries

and the body's cells.

Additional readings.

Gaseous Exchange In The Body

The exchange of Oxygen (O2) and Carbon Dioxide (CO2) between alveolar air andpulmonary blood occurs via passive diffusion. This is governed by the behavior of gases asdescribed by Dalton's Law and Henry's Law.

Gaseous exchange in the body occurs in two places:

1. Between the air in the alveoli of the lungs and the blood in pulmonary capillaries

(External respiration).2. Between the systemic capillaries and tissue cells (Internal respiration).

External Respiration

This process results in the conversion of deoxygenated blood from the right side of the heart

to oxygenated blood returning to the left side of the heart. Gases are exchanged bydiffusion according to the differences in their partial pressures.The now deoxygenated blood returns to the heart and is pumped to the lungs where the

process of external respiration begins again.The partial pressure of O2 in alveolar air is 105mmHg, while the resting partial pressure ofO2 in deoxygenated blood is ~40mmHg. Due to this difference O2 diffuses down its

concentration gradient from the alveolar air into the deoxygenated blood until equilibrium isreached, the result being that the blood becomes oxygenated.The partial pressure of CO2 in alveolar air is 40mmHg, while in deoxygenated blood it is 45mmHg. CO2 therefore diffuses in the opposite direction to O2, again down its concentration

gradient. The result being that CO2 is removed from the blood and exhaled.The now deoxygenated blood returns to the heart and is pumped to the lungs where theprocess of external respiration begins again.

The rate of gas exchange during external respiration depends on several factors:

Partial pressure difference of the gases

Surface area available for gas exchange

Diffusion distance

Solubility and molecular weight of the gases

Internal Respiration

The process of internal respiration is much the same as external respiration, only the site inwhich it occurs is different. Internal respiration results in the conversion of oxygenated

blood (from the capillaries) to deoxygenated blood. Once again the gases are exchanged inaccordance with their partial pressures.

The partial pressure of O2 in capillary blood is ~100mmHg, whilst in the tissues it is ~40mmHg. Due to this difference O2 diffuses from the blood, through the interstitial fluid into

the tissue cells until the partial pressure of O2 in the blood decreases to ~40mmHg.


20/34

CO2 again diffuses in the opposite direction. The partial pressure of CO2 in the tissue cells is

45mmHg, whilst in the blood it is 40mmHg. Therefore, CO2 diffuses from the tissue cells

through the interstitial fluid into the blood until its partial pressure in the blood reaches~45mmHg.

The deoxygenated blood returns to the heart from where it is pumped to the lungs and theprocess of external respiration begins again.

Gaseous Exchange

Erythrocyte (red blood cells) in the mammalian body are filled with a globular protein called

Haemoglobin. This molecule consists of 4 polypeptide chains each with an Iron Haem group

in the centre. This Haem group is very important for gaseous exchange.Once the Erythrocyte, laden with Oxygen molecules, reaches some tissues which have

an Oxygendeficit, the following reaction occurs:

CO2 + H2O H2CO3 HCO3- + H +( = a reversible reaction)

This equation is catalysed by the highly efficient enzymecalled Carbonic Anhydrase. The

CO2 is absorbed into the red blood cell then in this equation it is reacted with water to makefirstly to Hydrogen Carbonate and then to Hydrogen Carbonate- ions and H+ ions. The

HCO3- ions are pumped out of the cell and are replaced with Cl- ions to keep the chargesbalanced.The next stage in this process is as follows:

H+ + HbO8 HHb+ + 4O2

Here I have used Hb for Haemoglobin for simplicity because Hemoglobin is actually many

thousands of molecules long.

This stage of the reaction involves the Hydrogen ions bonding with HbO8 (Oxygen bonded

with Haemoglobin). The Hydrogen ions displace the Oxygen molecules from the Haemgroups and allow the Oxygen molecules to come into solution in the red blood cell. Thesethen diffuse through the phospholipid bilayer membrane of the red blood cell and move intothe surrounding tissues where Oxygen is needed leaving the Hydrogen bonded with the

Haemoglobin acting as a spectator ion, as it is not actually used for anything.

Once this reaction has occurred there will be Oxygen in the tissues and the Carbon Dioxide

which was in the tissues will now be carried back to the lungs to be exchanged for more

Oxygen.This reaction is entirely reversible and the opposite reaction happens at the lung to absorbnew Oxygen.


21/34


22/34

Enzymes are very efficient catalysts for biochemical reactions. They speed up reactions by

providing an alternative reaction pathway of lower activation energy.

Like all catalysts, enzymes take part in the reaction - that is how they provide an alternativereaction pathway. But they do not undergo permanent changes and so remain unchanged at

the end of the reaction. They can only alter the rate of reaction, not the position of theequilibrium.

Most chemical catalysts catalyse a wide range of reactions. They are not usually veryselective. In contrast enzymes are usually highly selective, catalysing specific reactions

only. This specificity is due to the shapes of the enzyme molecules.Many enzymes consist of a protein and a non-protein (called the cofactor). The proteins in

enzymes are usually globular. The intra- and intermolecular bonds that hold proteins in their

secondary and tertiary structures are disrupted by changes in temperature and pH. Thisaffects shapes and so the catalytic activity of an enzyme is pH and temperature sensitive.

Cofactors may be:

organic groups that are permanently bound to the enzyme (prosthetic groups)

cations - positively charged metal ions (activators), which temporarily bind to the

active site of the enzyme, giving an intense positive charge to the enzyme's protein organic molecules, usually vitamins or made from vitamins (coenzymes), which are

not permanently bound to the enzyme molecule, but combine with the enzyme-substrate complex temporarily.

How Enzymes WorkFor two molecules to react they must collide with one another. They must collide in the right

direction (orientation) and with sufficient energy. Sufficient energy means that between

them they have enough energy to overcome the energy barrier to reaction. This is calledthe activation energy.

Enzymes have an active site. This is part of the molecule that has just the right shape and

functional groups to bind to one of the reacting molecules. The reacting molecule that bindsto the enzyme is called the substrate.

An enzyme-catalysed reaction takes a different 'route'. The enzyme and substrate form areaction intermediate. Its formation has a lower activation energy than the reaction

between reactants without a catalyst.A simplified picture

Route A reactant 1 + reactant 2 ----------- productRoute B reactant 1 + enzyme ------------intermediate

intermediate + reactant 2 ---------------- product + enzymeSo the enzyme is used to form a reaction intermediate, but when this reacts with another

reactant the enzyme reforms.

Lock and Key Hypothesis

This is the simplest model to represent how an enzyme works. The substrate simply fits intothe active site to form a reaction intermediate.


23/34

Induced fit hypothesis

In this model the enzyme molecule changes shape as the substrate molecules gets close.The change in shape is 'induced' by the approaching substrate molecule. This more

sophisticated model relies on the fact that molecules are flexible because single covalentbonds are free to rotate.

Factors affecting catalytic activity of enzymes

Temperature

As the temperature rises, reacting molecules have more and more kinetic energy. This

increases the chances of a successful collision and so the rate increases. There is a certaintemperature at which an enzyme's catalytic activity is at its greatest (see graph). This

optimal temperature is usually around human body temperature (37.5 oC) for the enzymes

in human cells.Above this temperature the enzyme structure begins to break down (denature) since athigher temperatures intra- and intermolecular bonds are broken as the enzyme molecules

gain even more kinetic energy.

ph


24/34

Each enzyme works within quite a small pH range. There is a pH at which its activity isgreatest (the optimal pH). This is because changes in pH can make and break intra- and

intermolecular bonds, changing the shape of the enzyme and, therefore, its effectiveness.

he rate of an enzyme-catalysed reaction depends on the concentrations of enzyme and

substrate. As the concentration of either is increased the rate of reaction increases (seegraphs). For a given enzyme concentration, the rate of reaction increases with increasingsubstrate concentration up to a point, above which any further increase in substrate

concentration produces no significant change in reaction rate. This is because the active

sites of the enzyme molecules at any given moment are virtually saturated with substrate.The enzyme/substrate complex has to dissociate before the active sites are free toaccommodate more substrate.

Provided that the substrate concentration is high and that temperature and pH are kept

constant, the rate of reaction is proportional to the enzyme concentration.

Inhibition of enzyme activity

Some substances reduce or even stop the catalytic activity of enzymes in biochemicalreactions. They block or distort the active site. These chemicals are called inhibitors,

because they inhibit reaction.Inhibitors that occupy the active site and prevent a substrate molecule from binding to the

enzyme are said to be active site-directed(or competitive, as they 'compete' with the

substrate for the active site).Inhibitors that attach to other parts of the enzyme molecule, perhaps distorting its shape,

are said to be non-active site-directed(or non competitive).Immobilized enzymes

Enzymes are widely used commercially, for example in the detergent, food and brewingindustries. Protease enzymes are used in 'biological' washing powders to speed up thebreakdown of proteins in stains like blood and egg. Pectinase is used to produce and clarify

fruit juices. Problems using enzymes commercially include:

they are water soluble which makes them hard to recover

some products can inhibit the enzyme activity (feedback inhibition)


25/34

Enzymes can be immobilized by fixing them to a solid surface. This has a number of

commercial advantages:

the enzyme is easily removed

the enzyme can be packed into columns and used over a long period

speedy separation of products reduces feedback inhibition thermal stability is increased allowing higher temperatures to be used higher operating temperatures increase rate of reaction

There are four principal methods of immobilization currently in use:

covalent bonding to a solid support adsorption onto an insoluble substance

entrapment within a gel encapsulation behind a selectively permeable membrane

How Do Enzymes Function?

Enzymes are "biological catalysts." "Biological" means the substance in question is produced

or is derived from some living organism. "Catalyst" denotes a substance that has the abilityto increase the rate of a chemical reaction, and is not changed

or destroyed by the chemical reaction that it accelerates.

Generally speaking, catalysts are specific in nature as to the type of reaction they cancatalyze. Enzymes, as a subclass of catalysts, are very specific in nature. Each enzyme can

act to catalyze only very select chemical reactions and only with very select substances. An

enzyme has been described as a "key" which can "unlock" complex compounds. An enzyme,

as the key, must have a certain structure or multi-dimensional shape that matches aspecific section of the "substrate" (a substrate is

the compound or substance which undergoes the change). Once these two componentscome together, certain chemical bonds within the substrate molecule change much as a lockis released, and just like the key in this illustration, the enzyme is free to execute its duty

once again.

Many chemical reactions do proceed but at such a slow rate that their progress would seem

to be imperceptible at normally encountered environmental temperature. Consider for

example, the oxidation of glucose or other sugars to useable energy byanimals and plants. For a living organism to derive heat and other energy from sugar, thesugar must be oxidized (combined with oxygen) or metabolically "burned"

However, in a living system, the oxidation of sugar must meet an additional condition; thatoxidation of sugar must proceed essentially at normal body temperature. Obviously, sugar

surrounded by sufficient oxygen would not oxidize very rapidly at this temperature. In

conjunction with a series of enzymes created by the living organism, however, this reactiondoes proceed quite rapidly at temperatures up to 100F (38C). Therefore, enzymes allowthe living organism to make use of the potential energy contained in sugar and other food

substances.

Enzymes or biological catalysts allow reactions that are necessary to sustain life proceed


26/34

relatively quickly at the normal environmental temperatures. Enzymes often

increase the rate of a chemical reaction between 10 and 20 million times what the speed of

reaction would be when left uncatalyzed (at a given temperature).Nutrients locked in certain organics are complex macromolecules, or in hard-to-digest

matrices may be released or predigested by a high degree of heat or concentrated acidtreatment. In an alternative manner, specific enzymes can promote the pre-digestion of

certain complex nutrients and facilitate the release of highly digestible nutrients in organicsduring processing without the need of excessive heat or rigorous chemical treatment.

Transmission of Nerve Impulses

The transmission of a nerve impulse along a neuron from one end to the other occurs as aresult of chemical changes across the membrane of the neuron. The membrane of an

unstimulated neuron is polarizedthat is, there is a difference in electrical charge between

the outside and inside of the membrane. The inside is negative with respect to the outside

Polarization is established by maintaining an excess of sodium ions (Na+) on the outsideand an excess of potassium ions (K+) on the inside. A certain amount of Na+ and K+ is

always leaking across the membrane through leakage channels, but Na+/K+ pumps in the

membrane actively restore the ions to the appropriate side.

Other ions, such as large, negatively charged proteins and nucleic acids, reside within the

cell. It is these large, negatively charged ions that contribute to the overall negative charge

on the inside of the cell membrane as compared to the outside.

In addition to crossing the membrane through leakage channels, ions may also cross

through gated channels. Gated channels open in response to neurotransmitters, changes inmembrane potential, or other stimuli.

The following events characterize the transmission of a nerve impulseResting potential. The resting potential describes the unstimulated, polarized state of a

neuron (at about 70 millivolts).

Graded potential. A graded potential is a change in the resting potential of the plasma

membrane in the response to a stimulus. A graded potential occurs when the stimuluscauses Na+ or K+ gated channels to open. If Na+ channels open, positive sodium ions

enter, and the membrane depolarizes (becomes more positive). If the stimulus opens K+

channels, then positive potassium ions exit across the membrane and the membranehyperpolarizes (becomes more negative). A graded potential is a local event that does nottravel far from its origin. Graded potentials occur in cell bodies and dendrites. Light, heat,

mechanical pressure, and chemicals, such as neurotransmitters, are examples of stimulithat may generate a graded potential (depending upon the neuron).

Action potential. Unlike a graded potential, an action potential is capable of traveling long

distances. If a depolarizing graded potential is sufficiently large, Na+ channels in the triggerzone open. In response, Na+ on the outside of the membrane becomes depolarized (as in agraded potential). If the stimulus is strong enoughthat is, if it is above a certain threshold

leveladditional Na+ gates open, increasing the flow of Na+ even more, causing an action

potential, or complete depolarization (from 70 to about +30 millivolts). This, in turn,stimulates neighboring Na+ gates, farther down the axon, to open. In this manner, theaction potential travels down the length of the axon as opened Na+ gates stimulate


27/34

neighboring Na+ gates to open. The action potential is an all-or-nothing event: When the

stimulus fails to produce depolarization that exceeds the threshold value, no action potential

results, but when threshold potential is exceeded, complete depolarization occurs.

Repolarization. In response to the inflow of Na+, K+ channels open, this time allowing K+

on the inside to rush out of the cell. The movement of K+ out of the cell causes

repolarization by restoring the original membrane polarization. Unlike the resting potential,however, in repolarization the K+ are on the outside and the Na+ are on the inside. Soon

after the K+ gates open, the Na+ gates close.

Hyper polarization. By the time the K+ channels close, more K+ have moved out of the cell

than is actually necessary to establish the original polarized potential. Thus, the membrane

becomes hyperpolarized (about 80 millivolts).

Refractory period. With the passage of the action potential, the cell membrane is in an

unusual state of affairs. The membrane is polarized, but the Na+ and K+ are on the wrongsides of the membrane. During this refractory period, the axon will not respond to a new

stimulus. To reestablish the original distribution of these ions, the Na+ and K+ are returnedto their resting potential location by Na+/K+ pumps in the cell membrane. Once these ionsare completely returned to their resting potential location, the neuron is ready for another

stimulus.


28/34

The Synapse

The junction across which a nerve impulse passes from an axon terminal to a

neuron, muscle cell, or gland cell.

A synapse, or synaptic cleft, is the gap that separates adjacent neurons or a neuron and a

muscle. Transmission of an impulse across a synapse, from presynaptic cell to postsynapticcell, may be electrical or chemical. In electrical synapses, the action potential travels along

the membranes of gap junctions, small tubes of cytoplasm along the membranes of gapjunctions, small tubes of cytoplasm that allow the transfer of ions between adjacent cells. In

chemical synapses, action potentials are transferred across the synapse by the diffusion of

chemicals, as follows:

Calcium (Ca2+) gates open. When an action potential reaches the end of an axon, the

depolarization of the membrane causes gated channels to open that allow Ca2+ to enter.Synaptic vesicles release neurotransmitter. The influx of Ca2+ into the terminal end of the

axon causes synaptic vesicles to merge with the presynaptic membrane, releasing aneurotransmitter into the synaptic cleft.

Neurotransmitter binds with postsynaptic receptors. The neurotransmitter diffuses across

the synaptic cleft and binds with specialized protein receptors on the postsynapticmembrane. Different proteins are receptors for different neurotransmitters.

The postsynaptic membrane is excited or inhibited. Depending upon the kind of

neurotransmitter and the kind of membrane receptor, there are two possible outcomes forthe postsynaptic membrane, both of which are graded potentials.oIf positive ion gates open (which allow more Na+ and Ca2+ to enter than K+ to exit), the


29/34

membrane becomes depolarized, which results in an excitatory postsynaptic potential

(EPSP). If the threshold potential is exceeded, an action potential is generated.

oIf K+ or chlorine ion (Cl) gates open (allowing K+ to exit or Cl to enter), the membranebecomes more polarized (hyperpolarized), which results in an inhibitory postsynaptic

potential (IPSP). As a result, it becomes more difficult to generate an action potential onthis membrane.

The neurotransmitter is degraded and recycled. After the neurotransmitter binds to thepostsynaptic membrane receptors, it is either transported back to and reabsorbed by the

secreting neuron, or it is broken down by enzymes in the synaptic cleft. For example, thecommon neurotransmitter acetylcholine is broken down by cholinesterase. Reabsorbed and

degraded neurotransmitters are recycled by the presynaptic cell.Here are some of the common neurotransmitters and the kinds of activity they generate:

Acetylcholine (ACh) is commonly secreted at neuromuscular junctions, the gaps between

motor neurons and muscle cells, where it stimulates muscles to contract (by opening gated

positive ion channels). At other kinds of junctions, it typically produces an inhibitory

postsynaptic potential.Epinephrine, norepinephrine (NE), dopamine, and serotonin are derived from amino acids

and are secreted mostly between neurons of the CNS.

Gamma aminobutyric acid (GABA) is usually an inhibitory neurotransmitter (opening gated

Cl channels) among neurons in the brain.


30/34


31/34


32/34

Regulation of Digestion

The activities of the digestive system are regulated by both hormones and neural reflexes.

Four important hormones and their effects upon target cells follow.

Gastrin is produced by enteroendocrine cells of the stomach mucosa. Effects include

oStimulation of gastric juice (especially HCl) secretion by gastric glands.

oStimulation of smooth muscle contraction in the stomach, small intestine, and large

intestine, which increases gastric and intestinal motility.

oRelaxation of the pyloric sphincter, which promotes gastric emptying into the small

intestine.

Secretin is produced by the enteroendocrine cells of the duodenal mucosa. Effects include


33/34

oStimulation of bicarbonate secretion by the pancreas, which neutralizes the acidity of

chyme when released into the duodenum.

oStimulation of bile production by the liver.

oInhibition of gastric juice secretions and gastric motility, which, in turn, slows digestion inthe stomach and retards gastric emptying.

Cholecystokinin (CCK) is produced by enteroendocrine cells of the duodenal mucosa.

Effects include

oStimulation of bile release by the gallbladder.

oStimulation of pancreatic juice secretion.

oRelaxation of the hepatopancreatic ampulla, which allows flow of bile and pancreatic juices

into the duodenum.

Gastric inhibitory peptide (GIP) is produced by enteroendocrine cells of the duodenal

mucosa and causes the inhibition of gastric juice secretion and gastric motility, which, in

turn, slows digestion in the stomach and retards gastric emptying.

The second regulatory agent of the digestive system is the nervous system. Stimuli that

influence digestive activities may originate in the head, the stomach, or the small intestine.

Based on these sites, there are three phases of digestive regulation:

The cephalic phase comprises those stimuli that originate from the head: sight, smell,taste, or thoughts of food, as well as emotional states. In response, the following reflexes

are initiated:

oNeural response. Stimuli that arouse digestion are relayed to the hypothalamus, which, in

turn, initiates nerve impulses in the parasympathetic vagus nerve. These impulses innervate

nerve networks of the GI tract (enteric nervous system), which promote contraction of

smooth muscle (which causes peristalsis) and secretion of gastric juice. Stimuli that repress

digestion (emotions of fear or anxiety, for example) innervate sympathetic fibers that

suppress muscle contraction and secretion.

oGeneral effects. The stomach prepares for the digestion of proteins.

The gastric phase describes those stimuli that originate from the stomach. These stimuli

include distention of the stomach (which activates stretch receptors), low acidity (high pH),

and the presence of peptides. In response, the following reflexes are initiated:


34/34

oNeural response. Gastric juice secretion and smooth muscle contraction are promoted.

oHormonal response. Gastrin production is promoted.

oGeneral effects. The stomach and small intestine prepare for the digestion of chyme, and

gastric emptying is promoted.

The intestinal phase describes stimuli originating in the small intestine. These include

distention of the duodenum, high acidity (low pH), and the presence of chyme (especially

fatty acids and carbohydrates). In response, the following reflexes are initiated:

oNeural response. Gastric secretion and gastric motility are inhibited (enterogastric reflex).

Intestinal secretions, smooth muscle contraction, and bile and pancreatic juice production

are promoted.

oHormonal response. Production of secretin, CCK, and GIP is promoted.

oGeneral effects. Stomach emptying is retarded to allow adequate time for digestion

(especially fats) in the small intestine. Intestinal digestion and motility are promoted.

human physiology.docx

Documents