Editing Renal lecture notes

*started here on 03/22/10.

==Kidney I Structure and function overview==

====Functions of the kidney====
*It eliminates metabolic wates products like creatin, creatinine, and urea, as well as uric acid.
*It also does lots of other stuff:
**It controls the amount of water in the body and therefore regulates blood volume and therefore pressure.
**The kidney also regulates the circulating electrolyte balance.
***This is closely linked to regulation of water retention.
**It regulates acid / base.
***We'll have a whole lecture on this at the end of this section because the lungs are highly involved also.
**Production of specific hormones and enzymes
***This includes bone morphogens
***Prostaglandins can mediate vascular diameter; they also do lots of stuff in the kidney.
***Kallikrein and prostaglandins are important for transport phenomenons.
****These two are generated where they are needed and cleared quickly.
***IGF1 is important during kidney development.  It is not all that important in adults unless a kidney is removed or diseased.  If you remove the kidney, then remaining kidney will produce IGF1.  IGF1 is involved in renal hypertrophy.  The remaining kidney will grow in size.
**Specialized metabolic function (a catch-all phrase)
***Conversion of vitamin D to active from.
***The kidney can also generate ammonia from aas.
***It can synthesize glucose from non-carbohydrate sources.  Not a usual function; only under duress.
***It can inactivate small hormones by filtering them out and not reabsorbing them.

===Adrenal glands===
*These sit right on top of the kidneys.
*There are two types: the medulla (inner) and the cortex (outer) parts.
*The medulla generates norepi and epi.
*The cortex generates two classes of steroid hormones:
**Glucocorticoids:
***Involved in lots of intermediary metabolism.
**Metalocorticoids
***Adlosterone is most important.  It controls renal function.

===Kidney cross-section===
*No you don't have to know all bits and pieces.  Know:
**The cortex versus the medulla.  This is important for understanding how nephrons work.
**The striations are the individual tubules of the nephrons.
***There are about 1 million (half a million per kidney).

===Kidney bloodflow===
*This is a gross oversimplification.
*There is an artery and vein coming in.  They surround the tubular networks.  There is lots of branching because each tubule has its own vein and artery.
*The kidney receives a quarter of the cardiac output.
**This comes out to 1200 ml per minute in an adult male.
*Everything the kidney does depends on the first filtration of the blood.

===Renal nephrons===
*Nephrons cannot regenerate so if we lose them from ischemia or something, they cannot be regenerated.
**If you have damage to a nephron, you can repair it.
*We have lots of spares, so we can (and will) lose thousands throughout life.
*One will have normal function of the kidneys with only 1/3 the nephrons with which we start.
*Upon donation of a kidney, the remaining kidney will hypertrophy.
**The nephrons will get larger, not proliferate.
**This will restore about 80% of function.
*The kidney filters the blood, then the filtrate which contains small molecular weight things and water, and the nephron will selectively reabsorb stuff.
**What isn't reabsorbed is urine.
*The overall structure of the nephtron:
**The blood supply comes into the glomerular capillary bed.
**Then there is the tubule and the collecting duct.
**First we'll talk about the filtering unit and then of the tubule and collecting duct.

===Renal capsule = glomerulus and the capsule that contains it===
*There are two capillary beds in the kidney.
*The first capillary bed occurs in each of the glomeruli.
*This first capillary bed is a filtration system.
*The blood comes in through the afferent arteriole toward the efferent arteriole (A before E).
**The afferent arteriole is larger in diameter than the efferent arteriole.  This puts pressure on the filtering unit which drives water and low-molecular weight compounds '''out''' of the blood supply into the capsular space.
*The filtration unit is very specialized:
**The first filtration level is the endothelial cells.
***The fenestrations of the endothelial cells are negatively charged to repel proteins (which are generally positively ch,arged) so that the slits don't get clogged.
***These will let about anything except cells go through.
***That is why you have to have the charge because you don't want all the proteins to clogg.
**The second filtration level is the basemement membrane on which the endothelial cells sit (the deep membrane).
**The last specialization are the podocytes.  They sit on the outside of the capillary and have feet that interact with other podocytes to form very small slits (filtration slits).  These give the most selective (smallest) filter.

===Glomerular nephritis===
*When you lose the selectivity of filtration (allowing larger molecular weight components to enter the filtrate), there is no way to reabsorb those large things.
**Thus you will see proteins and such in the urine.
*This is usually caused by autoimmune disorders.
**This can occur during streptococcus infections, especially because the antibodies genreated in response can clog the filter.
*When you start filtering out proteins:
**the tubule can become blocked because the filtrate can become very viscus
**the proteins are removed from the blood such that osmotic pressure drops, thus causing adema throughout the body (look for adema in renal disorders).
***Once adema starts, one requires dialysis.
**Note that we all excrete proteins in the urine some times; it is not always indicative of disease.

===Post-filtrate formation===
*The filtrate enters the capsule and enters the tubule and on to the proximal convoluted tubule, loop of henle, distal convoluted tubules, and collecting duct.
**We distinguish between these four parts because different things occur in each.
*Nephrons come in two varieties:
**Cortical nephrons
***80-90% is in the cortex.
***Just a small part of the loop drops into the medulla.
**Juxtamedullary nephrons
***The loop drops all the way down into the urine.
***These are the nephrons that generate concentrated urine.

===Renal epithelial cells===
*All the segments are lined with epithelial cells but they are not all the same.
**The nature of the epithelial cells in each segment that determines the function of the segment.
*The apical surface of the epithelial cells is the side that face in toward the lumen of the tube.  Therefore the basolateral side is the opposite.
*Tight junctions between the epithelial cells keep filtrate and blood from flowing together between the cells.
*Secretion is from the blood to the lumen.  Absorption is from the lumen into the blood.  '''It is all relative to the blood.'''
*The apical membrane of these epithelial cells has lots of microvilli to increase surface area.

===Distinguishing features of epithelial cells in various segments===
*What transporter are present and on which membrane do they reside.
**Depending on which membrane you put this on will determine whether you have a secretory or excretory cell.
**For example: sodium-potassium ATPase is always found on the basolateral membrane.  So if you're moving filtrate from the lumen into the blood, you put a sodium channel on the apical surface and put an Na-K ATPase on the basolateral membrane.  This way, the sodium will flow down it's gradient into the cell and then be pumped out.
**There are a couple of exceptions.
*What can go through the junctional complexes - tight versus leaky epithelia:
**In the proximal tubule, lots of water and some ions transport across the juction (a leaky epithelial) but in the distal it is very tight, nothing gets by.
*The size and shape of the cells.
**These characteristics will dominate what it can do.
**Podocytes are a type of epithelial cell.
**The cells that line the capsule are inert and simply keep the filtrate in the capsule.
**The proximal tubule cells are thick with lots of microvilli and mt.  70-90% of what is reabsorbed from the filtrate into the blood occurs in the proximal tubules.
**The cells of the loop of henle are thinner, with fewer microvilli.  They have a very specialized function.  They move water in one area and move sodium / chloride in another area.
**The distal tubule (which contains the juxtoglomerular apparatus, where the distal tubule interacts with the afferent arteriole) and the collecting duct have quite large cells with few microvilli because most everything that will be reabsorbed has been reabsorbed.  In this section there is hormonal control over what will be reabsorbed.
***Once in the collecting duct there are two types of cells.  Those with microvilli handle acids / bases.
**All this is just to say that the size and shape helps dictate function.

===Renal nerves and lymphatic vessels===
*There are lots of nerves which can serve to change diameter of afferent vessel.
*There are lymphatics to drain.

===Renal blood flow at nephron level===
*There is a boatload of branching because there are lots of little vessels that surround the tubule.
*The efferent arteriole starts after the glomerulus and splits into many branches that surround the tuble and then join together to flow into the venous system.
**The branches that surround the tubules are called the tubular capillary bed and is the second of the two capillary beds.
**This bed does all that we would expect, like exchange oxygen, etc.
*The capillaries that surround the juxtamedullary nephronic loops are called the vasa recta.

===Juxtaglomerular apparatus===
*This is where the distal tubule is in direct contact with the afferent arteriole.
*At the point of contact, the epithelial cells of the distal tubule are called macula densa and the smooth muscle cells that surround the tubule are called granular cells.
*The macula densa are osmosensors so they can sense the osmolarity of the filtrate in this late stage of the nephron (after most stuff has been reabsorbed).  They can secrete factors that will affect constriction or dilation of the afferent vessel.  Constriction reduces blood flow and thus there is less filtrate.  Dilations causes increased blood flow and increased filtration.
*In the '''efferent arterioles''', the cells are called granular cells.  When these cells are stimulated by systemic factors, they secrete renin into the blood supply.  This will affect cells throughout the whole body.  For now, know that it has a systemic affect and that the overall affect is vasoconstriction and salt and fluid retention.
**We'll review this often.

===Blood flow of the kidney===
*About 1200 ml / minute.
*About 10% of the blood volume becomes the initial filtrate.
**This works about to 120 ml / min or 170 liters / day.
**But we don't pee that much.
**The entire plasma volume is filtered about 60 times per day.
*The filtrate is mostly water along with anything under 10k MW, including ions, aas, sugars, metabolic wastes, etc.
**Albumin is about 60K MW and Hb is about 40K MW.
*The formation of the filtrate is nonselective.  However, our reabsorption is selective.
*We can either reabsorb stuff or secrete stuff through the epithelial cells of the nephron.
**We are particularly interested in secreting acids.

===Formation of urine==
*Three mechanisms:
**Glomerular filtration
***relatively nonselective
**Tubular reabsorption
**Tubular secretion

*passed out exams.
*stopped here on 03/22/10.