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.

White Blood Cells (leukocytes)

White blood cells

• are much less numerous than red (the ratio between the two is around 1:700),
• have nuclei,
• participate in protecting the body from infection,
• consist of lymphocytes and monocytes with relatively clear cytoplasm, and three types of granulocytes, whose cytoplasm is filled with granules.

Lymphocytes: There are several kinds of lymphocytes, each with different functions to perform , 25% of wbc The most common types of lymphocytes are

• B lymphocytes ("B cells"). These are responsible for making antibodies.
• T lymphocytes ("T cells"). There are several subsets of these:
  • inflammatory T cells that recruit macrophages and neutrophils to the site of infection or other tissue damage
  • cytotoxic T lymphocytes (CTLs) that kill virus-infected and, perhaps, tumor cells
  • helper T cells that enhance the production of antibodies by B cells

Although bone marrow is the ultimate source of lymphocytes, the lymphocytes that will become T cells migrate from the bone marrow to the thymus where they mature. Both B cells and T cells also take up residence in lymph nodes, the spleen and other tissues where they

• encounter antigens;
• continue to divide by mitosis;
• mature into fully functional cells.

Monocytes : also originate in marrow, spend up to 20 days in the circulation, then travel to the tissues where they become macrophages. Macrophages are the most important phagocyte outside the circulation. Monocytes are about 9% of normal wbc count

Macrophages are large, phagocytic cells that engulf

• foreign material (antigens) that enter the body
• dead and dying cells of the body.

Neutrophils

The most abundant of the WBCs. about 65% of normal white count  These cells spend 8 to 10 days in the circulation making their way to sites of infection etc  Neutrophils squeeze through the capillary walls and into infected tissue where they kill the invaders (e.g., bacteria) and then engulf the remnants by phagocytosis. They have two types of granules: the most numerous are specific granules which contain bactericidal agents such as lysozyme; the azurophilic granules are lysosomes containing peroxidase and other enzymes

Eosinophils : The number of eosinophils in the blood is normally quite low (0–450/µl). However, their numbers increase sharply in certain diseases, especially infections by parasitic worms. Eosinophils are cytotoxic, releasing the contents of their granules on the invader.

Basophils : rare except during infections where these cells mediate inflammation by secreting histamine and heparan sulfate (related to the anticoagulant heparin). Histamine makes blood vessels permeable and heparin inhibits blood clotting. Basophils are functionally related to mast cells.  . The mediators released by basophils also play an important part in some allergic responses such as hay fever and an anaphylactic response to insect stings.

Thrombocytes (platelets):

Thrombocytes are cellular derivatives from megakaryocytes which contain factors responsible for the intrinsic clotting mechanism. They represent fragmented cells  which contain residual organelles including rough endoplasmic reticulum and Golgi apparati. They are only 2-microns in diameter, are seen in peripheral blood either singly or, often, in clusters, and have a lifespan of 10 days.

Biological Functions are Extremely Sensitive to pH

• H+ and OH- ions get special attention because they are very reactive
• Substance which donates H+ ions to solution = acid
• Substance which donates OH- ions to solution = base
• Because we deal with H ions over a very wide range of concentration, physiologists have devised a logarithmic unit, pH, to deal with it
  • pH = - log [H⁺]
  • [H⁺] is the H ion concentration in moles/liter
  • Because of the way it is defined a high pH indicates low H ion and a low pH indicates high H ion- it takes a while to get used to the strange definition
  • Also because of the way it is defined, a change of 1 pH unit means a 10X change in the concentration of H ions
    • If pH changes by 2 units the H+ concentration changes by 10 X 10 = 100 times

• Human blood pH is 7.4
  • Blood pH above 7.4 = alkalosis
  • Blood pH below 7.4 = acidosis
• Body must get rid of ~15 moles of potential acid/day (mostly CO₂)
  • CO₂ reacts with water to form carbonic acid (H₂CO₃)
  • Done mostly by lungs & kidney
• In neutralization H⁺ and OH^- react to form water
• If the pH changes charges on molecules also change, especially charges on proteins
  • This changes the reactivity of proteins such as enzymes
• Large pH changes occur as food passes through the intestines.

Platelets

Platelets are cell fragments produced from megakaryocytes.

Blood normally contains 150,000 to 350,000 per microliter (µl). If this value should drop much below 50,000/µl, there is a danger of uncontrolled bleeding. This is because of the essential role that platelets have in blood clotting.

When blood vessels are damaged, fibrils of collagen are exposed.

• von Willebrand factor links the collagen to platelets forming a plug of platelets there.
• The bound platelets release ADP and thromboxane A2 which recruit and activate still more platelets circulating in the blood.
• (This role of thromboxane accounts for the beneficial effect of low doses of aspirin a cyclooxygenase inhibitor in avoiding heart attacks.)

ReoPro is a monoclonal antibody directed against platelet receptors. It inhibits platelet aggregation and appears to reduce the risk that "reamed out" coronary arteries (after coronary angioplasty) will plug up again.

Membrane Structure & Function

Cell Membranes

• Cell membranes are phospholipid bilayers (2 layers)
• Bilayer forms a barrier to passage of molecules in an out of cell
• Phospholipids = glycerol + 2 fatty acids + polar molecule (i.e., choline) + phosphate
• Cholesterol (another lipid) stabilizes cell membranes
• the hydrophobic tails of the phospholipids (fatty acids) are together in the center of the bilayer. This keeps them out of the water

Membranes Also Contain Proteins

• Proteins that penetrate the membrane have hydrophobic sections ~25 amino acids long
• Hydrophobic = doesn't like water = likes lipids
• Membrane proteins have many functions:
  • receptors for hormones
  • pumps for transporting materials across the membrane
  • ion channels
  • adhesion molecules for holding cells to extracellular matrix

cell recognition antigens

Phases of cardiac cycle :

1. Early diastole ( also called the atrial diastole , or complete heart diastole) : During this phase :

- Atria are  relaxed
- Ventricles are relaxed
- Semilunar valves are closed
- Atrioventricular valves are open
During this phase the blood moves passively from the venous system into the ventricles ( about 80 % of blood fills the ventricles during this phase.

2. Atrial systole : During this phase :

- Atria are contracting
- Ventricles are relaxed
- AV valves are open
- Semilunar valves are closed
- Atrial pressure increases.the a wave of atrial pressure appears here.
- P wave of ECG starts here
- intraventricular pressure increases due to the rush of blood then decrease due to continuous relaxation of ventricles.

The remaining 20% of blood is moved to fill the ventricles during this phase , due to atrial contraction.

3. Isovolumetric contraction : During this phase :

- Atria are relaxed
- Ventricles are contracting
- AV valves are closed
- Semilunar valves are closed
- First heart sound
- QRS complex.
The ventricular fibers start to contract during this phase , and the intraventricular pressure increases. This result in closing the AV valves , but the pressure is not yet enough to open the semilunar valves , so the blood volume remain unchanged , and the muscle fibers length also remain unchanged , so we call this phase as isovolumetric contraction ( iso : the same , volu= volume , metric= length).

4. Ejection phase : Blood is ejected from the ventricles into the aorta and pulmonary artery .

During this phase :

- Ventricles are contracting
- Atria are relaxed
- AV valves are closed
- Semilunar valves are open
- First heart sound
- Intraventricular pressure is increased , due to continuous contraction
- increased aortic pressure .
- T wave starts.

5. Isovolumetric relaxation:  This phase due to backflow of blood in aorta and pulmonary system after the ventricular contraction is up and the ventricles relax . This backflow closes the semilunar valves .

During this phase :

- Ventricles are relaxed
- Atrial are relaxed
- Semilunar valves are closed .
- AV valves are closed.
- Ventricular pressure fails rapidly
- Atrial pressure increases due to to continuous venous return. the v wave appears here. 
- Aortic pressure : initial sharp decrease due to sudden closure of the semilunar valve ( diacrotic notch) , followed by secondary rise in pressure , due to elastic recoil of the aorta ( diacrotic wave)  .
- T wave ends in this phase