Levels of Organization:

CHEMICAL LEVEL - includes all chemical substances necessary for life (see, for example, a small portion - a heme group - of a hemoglobin molecule); together form the next higher level

CELLULAR LEVEL - cells are the basic structural and functional units of the human body & there are many different types of cells (e.g., muscle, nerve, blood)

TISSUE LEVEL - a tissue is a group of cells that perform a specific function and the basic types of tissues in the human body include epithelial, muscle, nervous, and connective tissues

ORGAN LEVEL - an organ consists of 2 or more tissues that perform a particular function (e.g., heart, liver, stomach)

SYSTEM LEVEL - an association of organs that have a common function; the major systems in the human body include digestive, nervous, endocrine, circulatory, respiratory, urinary, and reproductive.

There are two types of cells that make up all living things on earth: prokaryotic and eukaryotic. Prokaryotic cells, like bacteria, have no 'nucleus', while eukaryotic cells, like those of the human body, do.

Chemical Controls of Respiration

A.    Chemoreceptors (CO2, O2, H+)

1.    central chemoreceptors - located in the medulla
2.    peripheral chemoreceptors - large vessels of neck

B.    Carbon Dioxide Effects

1.    a powerful chemical regulator of breathing by increasing H+ (lowering pH)
    
a. hypercapnia            Carbon Dioxide increases -> 
                        Carbonic Acid increases ->
                        pH of CSF decreases (higher H+)- >
                        
DEPTH & RATE increase (hyperventilation)

b. hypocapnia - abnormally low Carbon Dioxide levels which can be produced by excessive hyperventilation; breathing into paper bag increases blood Carbon Dioxide levels

C.     Oxygen Effects

1.    aortic and carotid bodies - oxygen chemoreceptors

2.    slight Ox decrease - modulate Carb Diox receptors
3.    large Ox decrease - stimulate increase ventilation
4.    hypoxic drive - chronic elevation of Carb Diox (due to disease) causes Oxygen levels to have greater effect on regulation of breathing

D.    pH Effects (H+ ion)

1.    acidosis - acid buildup (H+) in blood, leads to increased RATE and DEPTH (lactic acid)

E.    Overview of Chemical Effects

 Chemical                             Breathing Effect

increased Carbon Dioxide (more H+)     increase
decreased Carbon Dioxide (less H+)     decrease

slight decrease in Oxygen             effect CO2 system
large decrease in Oxygen             increase ventilation

decreased pH (more H+)                 increase
increased pH (less H+)                 decrease

The nephron of the kidney is involved in the regulation of water and soluble substances in blood.

A Nephron

A nephron is the basic structural and functional unit of the kidneys that regulates water and soluble substances in the blood by filtering the blood, reabsorbing what is needed, and excreting the rest as urine.

 Its function is vital for homeostasis of blood volume, blood pressure, and plasma osmolarity.

It is regulated by the neuroendocrine system by hormones such as antidiuretic hormone, aldosterone, and parathyroid hormone.

The Glomerulus

The glomerulus is a capillary tuft that receives its blood supply from an afferent arteriole of the renal circulation. Here, fluid and solutes are filtered out of the blood and into the space made by Bowman's capsule.

A group of specialized cells known as juxtaglomerular apparatus (JGA) are located around the afferent arteriole where it enters the renal corpuscle. The JGA secretes an enzyme called renin, due to a variety of stimuli, and it is involved in the process of blood volume homeostasis.

The Bowman's capsule surrounds the glomerulus. It is composed of visceral (simple squamous epithelial cells; inner) and parietal (simple squamous epithelial cells; outer) layers.

Red blood cells and large proteins, such as serum albumins, cannot pass through the glomerulus under normal circumstances. However, in some injuries they may be able to pass through and can cause blood and protein content to enter the urine, which is a sign of problems in the kidney.

Proximal Convoluted Tubule

The proximal tubule is the first site of water reabsorption into the bloodstream, and the site where the majority of water and salt reabsorption takes place. Water reabsorption in the proximal convoluted tubule occurs due to both passive diffusion across the basolateral membrane, and active transport from Na+/K+/ATPase pumps that actively transports sodium across the basolateral membrane.

Water and glucose follow sodium through the basolateral membrane via an osmotic gradient, in a process called co-transport. Approximately 2/3rds of water in the nephron and 100% of the glucose in the nephron are reabsorbed by cotransport in the proximal convoluted tubule.

Fluid leaving this tubule generally is unchanged due to the equivalent water and ion reabsorption, with an osmolarity (ion concentration) of 300 mOSm/L, which is the same osmolarity as normal plasma.

The Loop of Henle

The loop of Henle is a U-shaped tube that consists of a descending limb and ascending limb. It transfers fluid from the proximal to the distal tubule. The descending limb is highly permeable to water but completely impermeable to ions, causing a large amount of water to be reabsorbed, which increases fluid osmolarity to about 1200 mOSm/L. In contrast, the ascending limb of Henle's loop is impermeable to water but highly permeable to ions, which causes a large drop in the osmolarity of fluid passing through the loop, from 1200 mOSM/L to 100 mOSm/L.

Distal Convoluted Tubule and Collecting Duct

The distal convoluted tubule and collecting duct is the final site of reabsorption in the nephron. Unlike the other components of the nephron, its permeability to water is variable depending on a hormone stimulus to enable the complex regulation of blood osmolarity, volume, pressure, and pH.

Normally, it is impermeable to water and permeable to ions, driving the osmolarity of fluid even lower. However, anti-diuretic hormone (secreted from the pituitary gland as a part of homeostasis) will act on the distal convoluted tubule to increase the permeability of the tubule to water to increase water reabsorption. This example results in increased blood volume and increased blood pressure. Many other hormones will induce other important changes in the distal convoluted tubule that fulfill the other homeostatic functions of the kidney.

The collecting duct is similar in function to the distal convoluted tubule and generally responds the same way to the same hormone stimuli. It is, however, different in terms of histology. The osmolarity of fluid through the distal tubule and collecting duct is highly variable depending on hormone stimulus. After passage through the collecting duct, the fluid is brought into the ureter, where it leaves the kidney as urine.

Plasma:  is the straw-colored liquid in which the blood cells are suspended.

Plasma transports materials needed by cells and materials that must be removed from cells:

• various ions (Na⁺, Ca²⁺, HCO₃⁻, etc.
• glucose and traces of other sugars
• amino acids
• other organic acids
• cholesterol and other lipids
• hormones
• urea and other wastes

Most of these materials are in transit from a place where they are added to the blood

• exchange organs like the intestine
• depots of materials like the liver

to places where they will be removed from the blood.

• every cell
• exchange organs like the kidney, and skin.

The small intestine

Digestion within the small intestine produces a mixture of disaccharides, peptides, fatty acids, and monoglycerides. The final digestion and absorption of these substances occurs in the villi, which line the inner surface of the small intestine.

This scanning electron micrograph (courtesy of Keith R. Porter) shows the villi carpeting the inner surface of the small intestine.

The crypts at the base of the villi contain stem cells that continuously divide by mitosis producing

• more stem cells
• cells that migrate up the surface of the villus while differentiating into
  1. columnar epithelial cells (the majority). They are responsible for digestion and absorption.
  2. goblet cells, which secrete mucus;
  3. endocrine cells, which secrete a variety of hormones;
• Paneth cells, which secrete antimicrobial peptides that sterilize the contents of the intestine.

All of these cells replace older cells that continuously die by apoptosis.

The villi increase the surface area of the small intestine to many times what it would be if it were simply a tube with smooth walls. In addition, the apical (exposed) surface of the epithelial cells of each villus is covered with microvilli (also known as a "brush border"). Thanks largely to these, the total surface area of the intestine is almost 200 square meters, about the size of the singles area of a tennis court and some 100 times the surface area of the exterior of the body.

Incorporated in the plasma membrane of the microvilli are a number of enzymes that complete digestion:

• aminopeptidases attack the amino terminal (N-terminal) of peptides producing amino acids.
• disaccharidasesThese enzymes convert disaccharides into their monosaccharide subunits.
  • maltase hydrolyzes maltose into glucose.
  • sucrase hydrolyzes sucrose (common table sugar) into glucose and fructose.
  • lactase hydrolyzes lactose (milk sugar) into glucose and galactose.

Fructose simply diffuses into the villi, but both glucose and galactose are absorbed by active transport.

• fatty acids and monoglycerides. These become resynthesized into fats as they enter the cells of the villus. The resulting small droplets of fat are then discharged by exocytosis into the lymph vessels, called lacteals, draining the villi.

Glomerular filtration

Kidneys receive about 20% of cardiac output , this is called Renal Blood Flow (RBF) which is approximatley 1.1 L of blood. Plasma in this flow is about 625 ml . It is called Renal Plasma Flow (RPF) .
About 20 % of Plasma entering the glomerular capillaries is filtered into the Bowman`s capsule .
Glomerular filtration rate is about 125 ml/min ( which means 7.5 L/hr and thus 180 L/day) This means that the kidney filters about 180 liters of plasma every day.

The urine flow is about 1ml/min ( about 1.5 liter /day) This means that kidney reabsorbs about 178.5 liters every day .

Filtration occurs through the filtration unit , which includes :

1- endothelial cells of glomerular capillaries , which are fenestrated . Fenestrae are quite small so they prevent filtration of blood cells and most of plasma proteins .

2- Glomerular basement membrane : contains proteoglycan that is negatively charged and repels the negatively charged plasma proteins that may pass the fenestrae due to their small molecular weight like albumin . so the membrane plays an important role in impairing filtration of albumin .

3- Epithelial cells of Bowman`s capsule that have podocytes , which interdigitate to form slits .

Many forces drive the glomerular filtration , which are :

1- Hydrostatic pressure of the capillary blood , which favours filtration . It is about 55 mmHg .

2- Oncotic pressure of the plasma proteins in the glomerular capillary ( opposes filtration ) . It is about 30 mm Hg .

3- Hydrostatic pressure of the Bowman`s capsule , which also opposes filtration. It is about 15 mmHg .

The net pressure is as follows :

Hydrostatic pressure of glomerular capillaries - ( Oncotic pressure of glomerular capillaries + Hydrostatic pressure of the Bowman capsule):
55-(35+10)
=55-45
=10 mmHg .

Te glomerular filtration rate does not depend only on the net pressure , but also on an other value , known as filtration coefficient ( Kf) . The later depends on the surface area of the glomerular capillaries and the hydraulic conductivity of the glomerular capillaries.