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Physiology Lecture Outline: The Renal System
Overview
The kidneys essentially act as a filtering system for the blood. The functional unit of the kidney is the
nephron. It acts to filter the plasma component of blood, reabsorb substances that we need to keep in our
bodies and excrete the waste products (as urine) that we no longer need. There are approximately 1.25
million nephrons in each kidney.
The three basic processes of the urinary system are: Filtration (F), Reabsorption (R), and Secretion (S).
These processes are related to Excretion (E) by the equation: E = F - R + S.
Filtration is under several types of control (e.g., myogenic and tubuloglomerular feedback) that regulate
blood flow through the renal arterioles. Reabsorption involves movement of substances back into the
body and Secretion involves movement of substances from the body into the renal tubules (out of the
body using protein transporters. These processes exhibit saturation, specificity, and competition.
Clearance (ml/min) is an abstract concept that describes renal handling of a substance based only on
blood and urine analysis. See Fig 19-17. Clearance is widely used in clinical settings, so it’s a good idea
to understand what it means and how it is useful.
FUNCTIONS OF THE KIDNEYS
1. Regulation of Extracellular Fluid Volume
This contributes to Mean Arterial Pressure by controlling the total volume of blood in the body. If the
volume is too high, then more filtrate is excreted; if too low, fluid is conserved and excretion is decreased.
2. Regulation of Osmolarity
Osmolarity is controlled by changing the amount of water that is excreted in the urine. If excessive water
intake decreases plasma osmolarity below 280 mOsM, the kidneys remove the excess water by producing
dilute urine. If osmolarity goes up, the kidneys conserve water, producing more concentrated urine.
3. Maintenance of Ion Balance
These are the usual suspects: Na+, K+, Cl-, Ca2+, H+, Mg2+, PO44. Homeostatic regulation of pH in body fluids
Selective secretion of H+ or HCO3- in the distal convoluted tubule of the nephron is how the kidney
contributes to the maintenance a stable pH.
5. Excretion of Wastes Products
Elimination of waste that is always accumulating in the body. Substance like Urea (a product of protein
catabolism), Uric Acid (a product of nucleic acid catabolism) are continuously excreted.
6. Excretion of Foreign Substances
Elimination of drugs, chemicals (pesticides, preservatives), bacterial or viral organisms from the body.
7. Production of Hormones
Renin - released in response to decreased blood osmolarity, signals salt and water retention by kidneys.
Erythropoiten - increases RBC production in the bone morrow.
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GENERAL ANATOMY OF THE URINARY SYSTEM
The 2 Kidneys are on either side of the spine, at 11th and 12th ribs, just above the waist. They are
retroperitoneal and linked to the urinary bladder by ureters. The bladder stores urine and is connected to
outside environment by urethra. Urine is stored until released (micturition) through the urethra by reflex.
The kidneys receive 20-25% of cardiac output, this is a large amount, consider that the brain only gets
about 20 % of cardiac output too. This large amount is necessary for their filtration role.
The Kidney has an Outer portion = Cortex; and an Inner portion = Medulla
The cortex is where the renal corpuscles are located. The medulla is characterized by higher-than-normal
ECF osmolarity that allows water reabsorption and the formation of concentrated urine.
In the nephron, the first capillary bed (the glomerulus) is for filtration only and the second capillary bed
(the peritubular capillaries) are for bulk reabsorption of fluid.
Arterial blood flow to and from nephron:
Afferent arteriole –> Glomerulus –> Efferent arteriole –> Peritubular capillaries –> Venous return
The capillary endothelium of glomerulus is fused to the epithelium of Bowman's capsule, so the fluid
filters directly from capillaries into tubule lumen. Water and molecules that filter out of the blood at the
glomerular capillaries do not go into the interstitial fluid as they do in other systemic capillaries.
The Nephron has 2 major components:
1. Renal Corpuscle = Glomerulus + Bowman's space + Bowman's capsule.
2. Renal Tubule is an epithelial lined tube which allows for the modification of the fluid (filtrate) as it
flows through the tubules toward the collecting duct.
The Renal Tubule = Proximal Convoluted Tubule, Loop of Henle and Distal Convoluted Tubule.
(continues on to –> Collecting duct –> Renal pelvis (fluid is urine by this time) –> Urinary bladder)
A portion of the distal convoluted tubule passes between afferent and efferent arterioles. This entire
arrangement is called the Juxtaglomerular Apparatus. It is a paracrine form of communication that
affects kidney autoregulation.
KIDNEY FUNCTION
Glomerular Filtration rate (GFR) is 180 L/day. This means that 180L of filtrate move through the
nephrons each day. However, 99% of filtered fluid re-enters the blood (is reabsorbed) so that only 1.5L of
filtrate actually leaves the body each day as urine (1.5L/day is excreted).
The 3 Processes of the Nephron are:
1) Filtration
2) Reabsorption
3) Secretion
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FILTRATION - Movement of fluid from blood capillaries of glomerulus to lumen of nephron. The fluid
is called filtrate once it has entered the nephron and when in the lumen, it's considered outside of the
body. Relatively nonspecific process. Filtrate = Plasma - (proteins, blood cells).
Not all small molecules in the plasma will be filtered. For example, low molecular weight fatty acids and
some Ca2+ ions bind to plasma proteins and therefore will not filter freely.
Barriers to Filtration: The arrangement of the Renal Corpuscle is such that there are essentially 3 layers
or barriers that molecules must pass through in order to become filtrate
1. Glomerular capillary endothelium, basal lamina, Bowman's capsule epithelium. Glomerular capillaries
are fenestrated with large pores. Thus, Almost all but blood cells and plasma proteins filters through.
2. The basement membrane of the fenestrated capillary bed. The Basal lamina is acellular and acts as a
coarse sieve (strainer) for molecules. Also, the slightly negatively-charged glycoproteins and collagenlike material of the basement membrane repels big negatively charged proteins.
3. The Bowman's capsule epithelium surrounding capillaries consists of podocytes (foot process cells),
which create narrow 'filtration slits'. The width of these slits can change the surface area that is available
for filtration. When podocytes contract, they increase the area available for passage of plasma, thus
increasing the rate of filtration.
Only about 1/5 of kidney plasma volume filters into nephrons = Filtration fraction. The remaining 4/5
moves into peritubular capillaries.
Filtration Occurs Because of Hydrostatic Pressure in the Capillaries
Glomerular filtration is similar to filtration out of systemic capillaries
1. Hydrostatic Pressure of blood forces blood out of leaky capillary epithelium (55 mm Hg)
2. Colloid Osmotic Pressure (COP) in capillaries vs COP of fluid within Bowman's (gradient of 30 mm
Hg) opposes fluid movement into capsule (favors reabsorption back into capillaries).
3. Hydrostatic pressure from Bowman's capsule (gradient of 15 mm Hg) opposes fluid movement into
capsule
Overall, there is a Net driving force is 10 mm Hg in favor of filtration. [55 + (-30) + (-15) = +10]
Glomerular Filtration Rate (GFR) remains constant over a mean arterial pressure (MAP) range of 80-180
mm Hg. The control of GFR is accomplished primarily by regulation of blood flow through the renal
arterioles. If renal arteriole resistance increases, renal blood flow decreases and blood is diverted to other
organs.
Effect of increased resistance on GFR depends on where the resistance change takes place. If resistance
increases in the afferent arteriole, hydrostatic pressure decreases on the downstream side of the
constriction and GFR decreases. If resistance increases in the efferent arteriole, blood "dams up" in front
of the increases resistance so that hydrostatic pressure and GFR increase. Most regulation occurs at the
afferent arteriole.
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GFR is Subject to Autoregulation
Autoregulation is a local control process in which the kidney maintains a relatively constant GFR in the
face of normal fluctuations in blood pressure.
1. Autoregulation of GFR via Myogenic Response.
The GFR is held constant at 180L/day within the mean arterial pressure range of 80 to 180 mm Hg. This
consistency is maintained by reflex control from Autonomic nervous system and hormones that affect the
diameter of the afferent and efferent arterioles.
Myogenic Response
If MAP increases, the smooth muscle in the wall of arterioles are stretched. In response to this stretching,
the smooth muscle contracts (the myogenic response), leading to vasoconstriction of the arteriole.
Vasoconstriction reduces blood flow through arteriole (and glomerulus) and in this way maintains a
constant volume of filtrate produced despite changes in MAP.
2. Tubuloglomerular Feedback
Portions of the distal convoluted tubule (DCT) pass between afferent and efferent arterioles. This area of
the DCT contains the Macula densa, which are modified cells in the tubule wall, which can exchange
information about the flow of filtrate to the arterioles. Juxtaglomerular cells (JG cells) are modified cells
in afferent (predominantly) arteriole walls. These cells synthesize and release renin - which is a hormone
involved in salt and water balance
A) Macula densa + JG cells = Juxtaglomerular apparatus
B) Tubuloglomerular feedback (Fig. 19-10):
A) Increased GFR: Increased distal tubule flow results in Macula densa sending a paracrine message to
afferent arteriole, causing constriction, this increases resistance which decreases blood flow through the
glomerulus and thus GFR decreases.
B) Exact stimulus initiating macula densa response is still unclear:
a. Some aspect of NaCl absorption at the macula densa.
b. Paracrine signals: Nitric oxide, adenosine.
Hormones and Autonomic Neurons Also Influence GFR
1. Sympathetic neurons, norepinephrine can affect afferent and efferent arterioles
Activation of  receptors causes vasoconstriction, but moderate sympathetic activity has little effect on
GFR. However, the sympathetic division of ANS can respond to drastic changes in systemic blood
pressure (hemorrhage, severe dehydration) decreases GFR.
2. Some of the hormones that influence arteriolar resistance and GFR:
a. Angiotensin II (AGII): Potent vasoconstrictor.
b. Prostaglandins: These are vasodilators.
c. Other actions: May alter filtration slit size by acting on podocytes or mesangial cells.