I. Anatomy of the kidney

A. Internal Anatomy

1. Cortex - outer region
2. Medulla - which has medullary (or "renal) pyramids
3. Renal columns - cortex that extends inward, separating pyramids
4. Renal pelvis - funnel like tube continuous with ureter
5. Calyces - branches off the pelvis, they collect urine
6. Ureter - the tube that branches off the kidney

B. Blood & Nerves

1. Renal arteries branch into segmental arteries - branch into local arteries - into interlobar arteries - arcuate arteries - interlobular arteries (pg 853)
2. Similar pattern for veins back to inferior vena cava
3. Nerves come from renal plexus - a bunch of autonomic nerves, the sympathetic of which help control renal blood flow

C. Nephrons - glomerulus, renal tubule, Bowman's capsule (see Fig. 26.5 & 26.8)

85% cortical nephrons (only the Loop of Henle dips into medulla)
15% are juxtamedullary nephrons, they lie deeper than the cortical nephrons

1. Nephron structure - capillary bed called glomerulus. It is covered by the end of the renal tubule called the Bowman's capsule. Fluid passes into the capsule from glomerulus. Renal tubules empty into collecting ducts.

a. Proximal convoluted tubule (PCT) - epithelium of PCT has microvilli - useful for absorbing substances and some secretions
b. Loop of Henle - has high permeability to water
c. Distal convoluted tubule (DCT) cells - do more secreting than reabsorbing.

2. Capillary beds of nephrons - glomerulus & peritubular capillaries.

a. Arterioles supply and drain glomerulus, so we refer to afferent and efferent arterioles.
b. Blood pressure is very high in the glomerulus forcing fluids and solutes into Bowman's capsule. 99% of this "filtrate" leaves the renal tubules and enters
c. Peritubular capillary beds. These branch off efferent arteriole. They have low pressure and are set up to make absorption easy. Supply the "secretions".
d. Peritubular beds of juxtamedullary nephrons have thin walled vessels parallel to Loops of Henle called vasa recta.

3. Juxtaglomerular apparatus (JGA). Just at the start of the DCT, at the top of the Loop of Henle, the tubule touches the afferent arteriole that serves its own renal corpuscle. Here tubule cells are crowded together forming the macula densa. These cells monitor NA+ and Cl- of fluid in tubule. Wall of arteriole in that region has modified smooth muscle called JG cells. JG cells & macula densa form the JGA which helps regulate arteriole BP & filtration rates.

A. Glomerular filtration - mechanical filter, not selective

1. The filtration membrane is the filter, 3 parts:

a. Fenestrated capillary endothelium - the pores in the capillaries of the glomerulus are too small to allow blood cells through.
b. The basement membrane - secreted by epithelial tissues. Its made of the basal lamina of the other two layers (a & c), fused.  Blocks most blood proteins except really small ones. Allows passage of particles up to 3 nm = water, glucose, amino acids, nitrogenous wastes. 7-9 nm blocked completely.
c. the spaces between the podocytes make up the third layer

2. Net filtration pressure. Glomerular filtration depends on 3 pressures, one that favors and 2 that oppose filtration.

a. Glomerular blood hydrostatic pressure

HPg = 55- 60 mm Hg

b. Capsular hydrostatic pressure

HPc = 15 mm Hg

This the back pressure caused by capsular walls & by fluid already in the renal tubule.

c. Blood colloid osmotic pressure or glomerular osmotic pressure.

OPg = 28-30 mm Hg

This is osmotic pressure, caused by water's tendency to move across a semi-permeable membrane toward the region of high solutes - in this case the solutes are plasma proteins that don't leave the blood.

Net filtration pressure

NFP = HPg - (OPg + HPc)
NFP = 60 - (28 + 15) or 55 (30 + 15) = 10 mm Hg
         = 17 mm Hg

So it isn't a very large pressure difference that gets filtration going.

3. Glomerular filtration rate, GFR = total filtrate produced per minute.

a. Related to: surface area, permeability & NFP. Normally around 120-125 ml/min.
b. GFR is directly proportional to NFP.

4. Regulation of glomerular filtration. GFR is dependent on blood flow in glomerular capillaries, which depends on systemic BP, and the diameters of afferent and efferent arterioles. 3 principle mechanisms: renal autoregulation, hormonal regulation and neural regulation.

a. Renal autoregulation - ability of kidneys to maintain constant BP despite fluctuation in systemic BP. Its intrinsic (operates w/in the kidneys). JGA is involved in a neg. feedback mechanism. If GFR is low, PCT and Loop of Henle absorb too much Na+ and Cl- and H2O. Macula densa cells detect low Na+ and Cl-. JGA cells are inhibited from producing their vasoconstrictor substance. Afferent arteriole then dilates, increasing HPg.

b. Hormonal regulation. Angiotensin II and atrial natriuretic peptide (ANP) are the two hormones.

1. Angiotensin II. Lower BP (and GFR) is detected by stretch receptors in the JGA. Juxtaglomerular cells secrete renin into the blood which, after a few biochemical steps we can skip becomes Angiotensin II. A II affects BP in several ways:
- vasoconstriction of arterioles
- it stimulates secretion of aldosterone by adrenal cortex. This leads to increased retention of Na+ and Cl- (+H2O), which raises BP.
- stimulates thirst center in hypothalamus
- stimulates ADH release from neurohypophysis
2. ANP. Increased blood volume stretches the atria and they secrete ANP. ANP is a diuretic, promotes excretions of Na+, suppresses ADH and more. All of these lower BP and should lower GFR but ANP actually increases GFR, either by dilating afferent arterioles or raising the permeability of the filter. (I think the current thought is that the permability change is the main effect)

c. Neural Regulation of GFR

- At rest - there is minimum sympathetic stimulation. Max dilation, max GFR.
- Moderate stimulation constricts afferent & efferent arteioles about the same, leading to slight increase in GFR.
- High sympathetic stimulation - much constriction of afferents decrease GFR. Blood goes elsewhere, therefor GFR could drop off to zero.

B. Tubular reabsorption. Substances are returned to the blood from the filtrate. These include glucose, amino acids, urea, Na+, K+, Ca++, Cl-, HCO3-, HPO4, and water by osmosis. Absorption of Na+ is especially important.   Most absorption takes place in the PCT, where epithelial cells have microvilli. The distal portions of the tubule are for fine tuning and secretion.

1. Reabsorption of Na+ in PCT.
- Conc. of Na+ is low inside tubule cell and its neg. charged inside relative to outside.
- Na+ diffuses from tubule fluid into cells through leakage channels.
- Sodium pumps expel Na+ to interstitial fluid.
- Na+ diffuses into peritubular capillaries.
- ATP is used - 6% of resting energy budget (about comparable to energy used for breathing while resting)
- Na+ pump also brings in K+ but it leaks out through numerous leakage channels.
- Water follows the Na+ due to osmosis.
- As water leaves filtrate, the concentration of remaining solutes increases, setting up a diffusion gradient for absorption of K+, Cl-, HCO3-.
- All that Na+ in peritubular capillaries make blood more + than tubular fluid, setting up electrical gradient for Cl- and HCO3-.

2. Reabsorption of nutrients in PCT.
- 100% of glucose, amino acids, lactic acid and other useful nutrients.
- Driven energetically by differences in ionic concentrations brought about by active transport, so this is referred to as secondary active transport.
- A symporter is a membrane protein that moves 2 or more substances in the same direction across a membrane.
-Glucose is an example: it enters PCT cell along with Na+.
- Substances entering this way leave PCT cells by facilitated diffusion, then enter capillary by simple diffusion.
- As with Na+, water "follows" these substances, also.

Symporter transport is limited. They can only go so fast. The limit is called the transport maximum, Tm (mg/min). If blood concentration of a substance is abnormally high, too much enters filtrate to all be absorbed and thus some of the substance ends up in the urine. Renal threshold of a substance is the plasma concentration at which the substance appears in urine because Tm has been exceeded. Renal threshold is in Mg/ml.

3. Reabsorption in Loop of Henle
- 30% of the K+, 20% Na+, 35% Cl-, 15% H2O
-In ascending part of Loop of Henle there are symporters that move one Na+, one K+, and two Cl- simultaneously - dependent on Na+ pumps.
- Na+ pumped out, K+ diffuses out, Cl- follows because of charge difference.
- Some water reabsorbed in descending limb of loop. Little or none in ascending loop - it's virtually impermeable to water.

4. Reabsorption in DCT and collecting ducts.
- At DCT, 80% of H2O has already been absorbed.
- Symporters in DCT transport Na+ & Cl-.
- At end of DCT - 90% of filtered solutes and water have been removed.
- That's 20L/day into collecting ducts ( a lot more than leaves as urine)
- ADH and aldosterone act on the "principal cells" of the final portion of DCT & of collecting ducts.
- Aldosterone (from the adrenal cortex) stimulates the principle cells to produce more sodium pumps, low aldosterone leads to Na+ being excreted along with water that follows it.
- ADH (from the hypothalamus) stimulates insertion of water channels into apical membranes of principle cells.  This allows the ready passage of water out of the tubule and into the blood.

5. Water reabsorption (this is kind of a recap of what I've said about water so far.

- Obligatory reabsorption accounts for 90% of H2O absorption. It's when H2O follows the solutes (osmosis). Occurs in PCT, descending loop, early DCT
- Facultative water reabsorption is water reabsorption in response to the body's needs. The main regulator is ADH, via negative feedback:

- we have osmoreceptors in hypothalamus
- they send nerve impulses to hypothalamus and neurohypophysis
- which leads to the release of ADH into blood.