Monday, 3 January 2011

On the Kidneys...


Thanks to all the make-up gurus on Youtube, I have lately been drinking water all the time. This has also made me pee all the time. If it does however make my skin glow, I’ll be thankful. Till then, let us analyse my reason to pee together (yes, fun times are ahead).

First, the structure of the main culprits – the Kidneys, there are two.



The kidney is surrounded by a tough capsule.

The outer part is the cortex and the inner is the medulla – this is similar to most organs. Your brain has a cortex and medulla too.

The Renal Pelvis is the lighter part in the centre where the urine meets to flow down the ureter. There it is stored in the bladder, till you decide its time for a visit to the pee house.

Where the action really happens…

Most of the kidney is made up of small tubules called nephrons surrounded with capillaries.

DEF: Nephron is the functional unit of the Kidney. It is a microscopic tubule that receives fluid from the blood capillaries in the cortex and converts it into urine which is then drained into the ureter.

 Each nephron starts at the cortex of the kidney. Here, the capillaries form a fine network called the glomerulus.

DEF: The glomerulus is a fine network of capillaries that increases local blood pressure to help squeeze the fluid out of the capillaries. It is surrounded by the Bowman’s capsule which collects the fluid and leads into the nephron.

The process by which the fluid is pushed into the Bowman’s capsule from the glomerulus is called Ultrafiltration.

Ultrafiltration

DEF: Ultrafiltration is filtration at a molecular level – molecules of a relative molecular mass under a certain amount are let in while the larger molecules are filtered out. In the Bowman’s capsule, molecules with a relative molecular mass of 69000 and under are allowed in.



Afferent vessels carry blood TO the organ.

Efferent vessels carry blood AWAY from the organ.


Both in this case, both are arterioles. Why?

Arterioles have muscular walls which can constrict to raise local blood pressure so the fluid can be forced out of the capillaries. The afferent is also wider in diameter than the efferent to increase pressure.


  
This pressure difference pushes fluid out of the blood in the glomerulus into the B. Capsule.


Imagine…

You are the fluid in the blood. You are now in the glomerulus. This is the path you would take.



You first need to cross the endothelium of the capillaries.

The endothelium of the capillaries has narrow gaps between the endothelial cells.

Through these gaps, you (the blood plasma) and the substances dissolved in you (amino acids, glucose, urea, inorganic ions like sodium, chloride and potassium) can pass through to leave the capillaries.

You have now left the glomerulus.

The next hurdle is the basement membrane. The basement membrane is a fine mesh of collagen fibres and glycoproteins which are a filter.

All molecules that are around you who are too fat (over 69,000 relative molecular mass) cannot pass through. Almost all proteins and ALL blood cells are too large to get through so they remain in the capillaries.  

You (the blood plasma) have now passed through the endothelium of the capillaries of the glomerulus and the basement membrane. With you are your smaller friends – the amino acids, glucose, urea and the inorganic ions like sodium, chloride and potassium.

Your last hurdle is the epithelium of the Bowman’s capsule. The epithelial cells are called podocytes.

Podocytes are specialised cells that make up the lining of the Bowman’s capsule.

They have finger-like projections called major processes that ensure gaps between cells and increase surface area.

Pass between the gaps of these cells are you are now in the lumen of the Bowman’s capsule.

Congratulations! You passed Ultrafiltration. J



After ultrafiltration, the capillaries are left with blood cells and proteins. Proteins ensure there is a negative water potential which means some fluid is retained in the capillaries. This low water potential allows for water’s re-absorption at a later stage.

NB: Since high blood pressure damages capillaries of the glomerulus and the epithelium of the Bowman’s capsule, the presence of proteins in urine can be a sign of hypertension.

Take a water break! Or a pee break!

Selective Reabsorption…

Most of the reabsorption occurs in the Proximal Convoluted Tubule (PCT).

All the glucose, amino acids are reabsorbed.

Some salts are reabsorbed.

Structure of PCT cells that specialised to achieve efficient reabsorption.



For simplicity, let us name the side of the cell in contact with the tubule fluid, the fluid side and the side near the blood capillary and tissue fluid, the bloody side.

The fluid side has microvilli. Microvilli are microscopic folds of the cell surface membrane that increase surface area for reabsorption.

Fluid side membrane also has co-transporter proteins. These proteins allow facilitated diffusion of simple ions to be accompanied by the transport of larger molecules like glucose. This simply means that these co-transporter proteins transport glucose or amino acids, along with sodium ions by facilitated diffusion (diffusion enhanced by proteins).

Bloody side membrane has folds to increase surface area. It also has Na+/K+ (sodium-potassium pumps) that pump Na+ out and K+ in. (NAOUT and KIN or just remember letters required for out (3) and Na+ also has three, while its 2 for K+ )

The PCT cell itself has many mitochondria as a lot of ATP is required for active processes.

Explaining the action involved…

Na+/K+ pumps on the bloody side remove Na+ ions from the PCT cell. Concentration of Na+ ions in cell decreases. This is an active process and requires ATP.

Na+/K+ pumps are protein pumps that pump Na+/K+ ions against their concentration gradients using energy from ATP.  

Na+ ions diffuse into cell across concentration gradient by facilitated diffusion from the fluid side. The co-transporter proteins also allow diffusion of glucose and amino acids along with the Na+ ions.

Concentrations of glucose and amino acids in the PCT cell increase. They diffuse out of cell into tissue fluid from the bloody side across a concentration gradient. This can be enhanced further with active removal of glucose and amino acids to the tissue fluid across bloody side.

These substances diffuse into the blood from the tissue fluid across a concentration gradient.

Reabsorption of these = increased water potential in tubule fluid = decreased water potential in tissue fluid

I.E. Water potential of fluid on bloody side <  Water potential of fluid on fluid side.

Therefore, water moves into cell from fluid side, into the tissue fluid and into the blood through osmosis.

Larger molecules like small proteins that may have been filtered are reabsorbed by endocytosis.

Water reabsorption

DEF: Osmoregulation is the regulation and control of water potential in blood and body fluids. In humans, the kidney does this.

After the PCT in the nephron comes the Loop of Henle. The Loop of Henle creates a low water potential in the medulla tissue (the cells around the nephron) so that more water can reabsorbed from the collecting duct.

The Structure of the Loop of Henle

The Hairpin countercurrent multiplier (see, women contribute to science too!)

This is the arrangement of the Loop of Henle in a sharp hairpin bend where one part of the tubule is close to another part of the tubule with the fluid flowing in opposite directions.

This helps create a high concentration of solutes because exchange of contents is allowed.



The top of the ascending limb therefore is left with very dilute urine. (Less gunk, more water)

When it leaves the ascending limb and enters the DCT (distal convoluted tubule) and collecting ducts, the water potential is high. So water can be reabsorbed back into the blood across a concentration gradient through osmosis.

The amount reabsorbed depends on the body’s needs, which is why the kidney plays the key role in Osmoregulation.

As you descend deeper into the medulla, the tissue fluid is lower in water potential due to the active removal of salts from the ascending limb.

Inside the Distal Convoluted Tubule…

Active transport is used to adjust concentrations of various salts.

(That is all for the DCT… no really!)

Inside the Collecting Ducts…

Since fluid still contains very dilute urine, it has a high water potential.

The collecting ducts descend back through the medulla to the pelvis. The deeper you descend, the lower the water potential the tissue fluid has. So as tubule fluid goes down the collecting ducts, water is lost to the tissue fluid through osmosis. Water then enters blood capillaries – by osmosis again.

Amount of water absorbed = body’s needs.

Also, amount of water absorbed = permeability of walls of collecting duct (we can control this!).

Osmoregulation…

Anti-diuretic hormone (ADH) is a hormone released from the posterior pituitary gland. It acts on the permeability of the collecting duct walls to increase their reabsorption of water.  

Posterior Pituitary Gland is the hind part of the pituitary gland which releases ADH.

If you are in the Sahara dessert and you forgot to take a water bottle..

You are low on water. Water potential of the blood is therefore low.

Osmoreceptors: Receptor cells that monitor the water potential of the blood.

On detection of low water potential, water moves out these cells by osmosis. They shrink and therefore stimulate the neurosecretory cells.

Neurosecretory cells: specialised neurones (nerve cells) that produce and release ADH.

Their cell bodies lie in the hypothalamus and their axon leads down to the terminal bulb which lies in the posterior pituitary gland. The ADH is produced in their cell bodies. It flows down axon and stores itself in the terminal bulb in the posterior pituitary gland. It is stored here until needed.

When osmoreceptors shrink and stimulate neurosecretory cells, action potentials are sent down the axons and ADH is released from the terminal bulb.  

If you were the ADH molecule instead…

You are made in the cell bodies of the neurosecretory cells which are in the hypothalamus. After being made, you flow down the axon and are stored in the terminal bulb in the posterior pituitary gland.

When water potential in the blood is low, osmoreceptors detect it and water leaves the cell by osmosis. Cells shrink and stimulate neurosecretory cells. Action potential is formed in the neurosecretory cell and sent down to terminal bulb that leads to your (ADH) release from the terminal bulb.

You enter the blood capillaries running through the posterior pituitary gland.

On reaching the cells of the wall of the collecting duct (your target cells), you bind yourself (the ADH hormone molecule) to the complimentarily shaped receptors bound to the membrane of the walls of the collecting duct.

You (ADH) cause a series of enzyme controlled reactions.

This causes vesicles with aquaporins or water permeable channels to fuse itself with the membrane making the membranes of the wall of the collecting duct more water permeable. Water can now move out of the collecting duct and be reabsorbed. The urine will be concentrated, with low water potential and pee will be a smaller volume.


If you move back into the hotel and sit in the AC and drink lots of fluids…

Less ADH is released into the blood. ADH only has the half-life of 20 minutes. Any present in the blood is broken down and cells of the walls of the collecting ducts are stimulated less.

The cell surface membranes of the cells of the collecting duct fold inwards to create vesicles of the aquaporins (similar to endocytosis).

Walls become less permeable, less water is reabsorbed and a large volume of dilute urine is produced.

Half-life of a substance is the time taken for its concentration to drop to half of its original value.

And what if Kidneys bail on you?

Reasons for Kidney Failure:
  • Diabetes mellitus (Type 1 or Type 2)
  • hypertension
  • infection

If kidneys fail, excess urea and salts cannot be removed. Osmoregulation cannot enter. You will eventually die.

Your options:

1. Dialysis

Dialysis is the filtration of blood using a partially permeable membrane.

This partially permeable membrane is called dialysis membrane. It separates the blood in the dialysis machine from the dialysis fluid.

Dialysis fluid is a complex solution with the same composition as body fluids.

Dialysis must be combined with a carefully monitored diet.

There are two types of dialysis.

  1. Haemodialysis is when the blood from a vein is passed through a dialysis machine. The blood and the dialysis fluid are separated by the dialysis membrane across which exchanges can happen. Heparin is used to prevent blood clotting and bubbles must be removed before the blood returns to the body. Dialysis is carried out about 3 times a week, each for several hours.


  1. Peritoneal Dialysis is when dialysis fluid is pumped into the body cavity so that exchange can occur across the body’s own partially permeable peritoneal membrane. A permanent tube is in the abdomen by a surgeon. Dialysis fluid is poured through this tube and fills the space between abdominal wall and other organs in the body cavity. After several hours, the used solution is drained from the body.



The other option is Kidney Transplant where, under general anaesthesia, a surgeon implants a new kidney into the lower abdomen and attaches to blood supply and bladder.

Advantages

·        Not time consuming and no weekly commitment.
·        Quality of life improves – less limited diet, ability to travel etc.
·        No longer chronically ill

Disadvantages

  • Immunosuppressants have to be used forever and make patient susceptible to other infections and diseases.
  • Organ rejection
  • Surgery risks – infection, bleeding, damage to other organs.
  • Anti-rejection medicines have side effects including fluid retention and high blood pressure.   

You are what you urinate…

Knowing what is up in your body when you visit a doctor usually involves a urine test. This is because substances produced in your body and released into your blood, if smaller than 69,000 relative molecular mass will be filtered in the glomerulus and turn up in your urine, if not reabsorbed.

How do you find out if you are knocked up?

We all know the basics. A bee bites the Mama when the Papa loves her and then a baby grows in Mama’s stomach. Or in other words, a sperm fertilises an egg (with no bees involved unless conception happened near plants or in a public park) and the embryo implants itself to the uterine lining.

Once this happens, the embryo starts secreting a hormone called human chorionic gonadotrophin (hCG). This glycoprotein molecule is smaller in molecular mass than 69,000 and can be detected in the urine.

A pregnancy test therefore, uses monoclonal antibodies which are specific and only bind to hCG. They are complimentarily shaped. If hCG molecules attach to the antibodies, the antibodies are tagged with a blue bead. These move up the strip until they reach a wall (band) of immobilised antibodies. The hCG-antibody complex sticks to the band forming a blue line.

A control blue line exists to use for comparison, the second indicates pregnancy.

Monoclonal antibodies are identical clones of one original cell.

How to know whether he is fit, or just full of steroids?

Anabolic steroids are drugs that mimic the action of the natural steroids that increase muscle growth. They are banned by all sporting bodies.

They have a half life of 16 hours so they can be detected in the blood for many days. They are small molecules with a relative molecular mass less than 69,000 so they can enter the nephron and end up in your urine. You can tests for their presence using gas chromatography.
Gas chromatography is a technique used to separate substance in a gaseous state. For all the fellow chemists, the idea is similar to that of mass spectroscopy – which can also be used alternatively.

Steps for gas chromatography:

  1. Sample is vaporised in presence of a gaseous solvent.
  2. It is passed along a long tube lined with an absorption agent.
  3. The amount of time the gas stays in the gas and is not absorbed onto the lining is specific to each substance. This is called the retention time.
  4. These results are analysed and form a chromatogram.

Chromatogram is a chart produced when substances are separated by the movement of a solvent along a permeable membrane like paper or gel.

Standard samples of drugs must run alongside a urine sample in gas chromatography so that we can compare their results and use them as markers to show their presence.


Websites used:





The OCR Biology Heinemenn textbook was also used for reference.