what are the functions of the kidneys
1.excretory -Urea and Creatinine -Drugs (must be water soluble) -toxins 2.Regulatory -H2O -electrolytes(Na,K,Cl,HCO,Ca) -pH 3.Endocrine -erythropoietin -renin (made by juxtaglomerular apparatus) -prostaglandin(regulates intrarenal circulation) 4.Metabolic -activates vit D adds OH to the first carbon (proximal convuluted tubule which have alpha 1 hydroxylase) This enzyme is regulated by parathyroid hormone
how does the body excrete non-polar drugs
since non-polar drugs cannot leave through the kidneys or the GI they must be biotransformed by the liver. Biotransformation can occur in 1 or 2 phases. Phase 1 reactions expose polar groups of nonpolar substances making them more polar. And phase 2 reactions add a polar cap. These reaction occur within hepatocytes but once they occur an active transporter is required to remove these, now polar substances, from the hepatocytes. They can either be moved to the biliary system where they will conjugate and be excreted via the GI tract or be moved to the circulatory system where they will be urinated out.
anatomy of nephron
anatomy of glomerulus
anatomy of peritubular capillary network
comparing anatomy of nephrons
about 10% of glomeruli are juxta
blood flow through the kidneys
about 1000 ml per min between two kidneys
400 ml of it is cells and the other is plasma that is being filtered
the 400 ml passes through and back into circulation
of the 600 ml 65% gets reabsorbed at the proximal convuluted tubule. Then 15% at the descending loop. non is absorbed at the ascending loop. and about 15% at the distal convuluted tubule. This leaves 5% of the 600 ml that we started with. Aldosterone(excretes potassium) and ADH can increase this reabsorption and normally do so that of the 600 ml 99% gets reabsorbed.
normal urine output
Under 500 is oliguria and above 3500 is polyuria. These numbers are b/c doctors wanted people to get a full 8 hours of sleep. And the kidney is able to concentrate waste at 1200 mmols per liter. Your body makes 600 mmols of waste product per day. Therefore you need atleast 500 ml output to get it out.
what is azotemia and what is uremia
azotemia is an increase in BUN and creatinine with normal kidney function. Uremia is Azotemia + signs of kidney failure
anatomy of the glomeruli
the afferent artery breaks into many capillaries which are anastomosed together. These capillaries are known as the glomeruler capillary tuft. (GCT) the GCT is surrounded by a double layered membrane. Partieral epithieal cells and visceral epithilial cells(podocytes). Together with the GCT they make up the glomeruli. This double layer together are known as the bowmans capsule. Inbetween the capillaries are mesangial cells which produce a mesangial matrix of connective tissue. The capillaries plus the mesangial cells plus the matrix is known as the mesangium. Between the capillaries and the podocyte is the basement membrane.The endothlial cells of the capillaires are fenestrated (1000s). Therefore they are called fenestrated capillaries. The middle of the basement membrane is very dense and is called lamina densa. The side toward the capillaries is known as the lamina rara interna and the side toward to bowmen capsule is the lamina rara externa
structure of the basement membrane
mostly made of collagen type 4 (triple helix of alpha peptide chains) each collagen type 4 has on its peptide chain a sequence known as globular noncollagenous component (GNC) this part can be attacked by autoantibodies. Causing inflammation of the basement membrane. (proteinuria/hematouria). This is known as anti GBM antibodies. Similar basement membrane in the alveloi leading to hemoptysis due to anti ABM antibodies. This is good pasture syndrome. If it only damages the kidney its anti GBM glomerulonephritis. GNC has a bunch of electronegatives substances within it making the entire basement membrane electronegative. There are also negativily charged molecules on the endothelium and podocytes.
Type 1: bONE
CarTWOlage-type 2 found in cartilage
type 3 is in many places
type 4 is under the floor (basement membranes)
glomerulus filteration process
blood moves into the glomerulus through the afferent artery. It is filtered through the fenestrations in the anastomosed capillaries. These fenestrations are about 70-100 nm in diameter. Next we move through the type 4 collagen basement membrane. attached to the bottom of the basement membrane is the visceral epithial cells of the bowmans capsule. These cells have foot processes which interconnect with each other forming slits (20-30 nm). Therefore smaller molecules can filter easier. Furthermore all 3 of these barriers are electronegative Therefore cations are attracted and move more easily.
types of protein filteration
Normally protein doesnt filter. WE have 3 main proteins from smallest to biggest... albumin, globulins, fibrogens. Albumins are small enough to pass through all 3 filtration barriers but since it and all other proteins are negativily charged they do not pass.
mesangial cells function
1.they can contract thereby influencing GFR
2.they can phagocytos preventing immune cells (complexes) from fucking up the charges and shit
3.they can proliferate (make their own Connective tissue matrix) in some diseases this process is overdone and it reduces blood flow of the capillaries
determined by forces favoring filteration subtracted by forces opposing filteration. It is also determined by the filteration coefficent (ksubf). The pressure in the glomerular capillaries are higher then normal capillaries. (hydrostatic pressure of 50mmhg vs 25 in normal capillaries)
what forces favor filteration
capillary pressure which is 50 mmhg
and the osmotic colloid pressure in the bowmans capsule which is usually 0
what forces apose filteration
the colloid osmotic pressure in the capillaries (30 mmhg)
hydrostatic pressure in bowmans space (10mmhg)
what is ksubf determined by
permeability of capillary membrane (hydrolic conductivity):basically the diameter of the fistulas of the capillary
Total surface area of filtering membrane: the number of filters
The product of these two = Ksubf
Since GFR is directly proportional to Net filteration pressure and Ksubf then GFR=Ksubf x net filteration pressure
calculating GFR. and what is filtration fraction
CO is 5L per min so 20% of this CO goes to kidneys per min. therefore 1 L goes to the kidney. 600 of this is plasma and 20% of this actually filtered so 120ml thats = GFR
Filtration fraction = GFR/renal plasma flow
what can cause a decrease in hydrolic conductivity (permeability)
an increase in the thickness of the glomerular capillary membrane (basement membrane) such as in DM and HTN
Decrease in total surface area such as in chronic pyelonephritis or glomerulonephritis
what factors can increase the forces that oppose filteration
1.an obstruction in the urinary system such as a crystal causing a backup of fluids into the bowmans space increasing the hydrosatic pressure.
2.Anything that increases the filteration fraction increases the colloid osmotic pressure in the capillaries b/c of hemoconcentration effect.
types of renal failure. Pre, intra, post
pre renal is when the kidneys arent getting enough perfusion.
Intrarenal is when the glomeruli are damaged
Post renal is when there is a problem with the drainage system such as an obstruction.
explain how hydrostatic pressure in the glomerular capillaries is effected
1.BP, diameter of afferent and efferent arteriole
when afferent ateriole is constricted GFR decreases... It has alot of alpha 1 adrenergic receptors which bind epi and norepi but also has receptors for endothelin.as for dilators we have nitric oxide, bradykinin, and prostaglandins
The Efferent artery has many angiotensin 2 receptors. normally constricting increases the Hydrostatic pressure and the GFR but if you constrict to much the hydrostatic pressure rises to much and it increases the filteration fraction causing the colloid osmotic pressure to rise and you get a net drop in GFR. Therefore we say there is biphasic change in GFR with efferent ateriole constriction.