Lecture 23

Handouts: 23A -- Basic Processes in Kidney Tubule -- posted on Courseworks
23B -- Kidney Structure

Oxytocin is not just for contractions! An article from NPR: When the 'Trust Hormone' is out of balance. http://www.npr.org/templates/story/story.php?storyId=126141922

I. Wrap up of Thyroid

Goiter & Graves Disease -- see notes of last time -- III-A.

II. Intro to Kidney Function (Handout 23A). See also Sadava Sect. 52.4 & 52.5 (51.4. & 51.5).

Here's an article from the LA Times on a recent artificial kidney.

A. Overall Function -- what does the kidney do?

1. Function: Controls water loss and determines what other specific components (including protons & other ions) will be excreted (lost in urine) and what will be retained.

2. What processes occur in kidney?

filtration

tubular secretion (addition of substances to the filtrate) = secretion into the tubule

tubular reabsorption (removal of substances from filtrate) = reabsorption from the tubule

control of volume of urine

B. Details of Basic Processes

1. Basic set up

a. Capillaries: Artery (from heart) → afferent arteriole → glomerular capillaries → efferent arteriole → peritubular capillaries → venule → vein (back to heart)

b. Filtration: Material moves from glomerular capillaries into tubule.

c. Secretion & Reabsorption: Materials moves between inside of tubule and inside of peritubular capillaries (surrounding kidney tubule).

2. The 4 Basic Processes

a. Filtration:

(1). Occurs in glomerulus

(2). About 20% of blood liquid (plasma) enters Bowman's capsule = filtrate

(3). Filtrate contains no large proteins or cells

b. Tubular (selective) secretion: Material is added to the filtrate.

(1): Terminology: Secretion is NOT the same as excretion.

Secretion = extruded by the cells into extracellular space (into filtrate, lumen, etc.).

Excretion = carried out of body in urine or feces.

(2). Result of filtration: filtrate carries high concentrations of certain dissolved materials (secreted by cells lining the lumen) -- removes waste, toxins from circulation.

c. Tubular (selective) reabsorption: Material is removed from the filtrate.

(1). Result of reabsorption: Filtrate does NOT carry certain materials (which are selectively reabsorbed) -- conserves valuable materials; returns them to circulation.

(2). Aldosterone affects Na⁺ reabsorption (& K⁺ secretion). Details below.

d. Volume Control:

(1). Water loss is adjusted at the end of the tubule using ADH. (See below.)

(2). Water loss or conservation in tubule controls volume of body fluids -- volume of plasma, extra cellular fluid, etc. (& blood pressure).

(3). Urine can be more -- or less -- concentrated than the plasma. Concentration and/or volume can be varied to suit need.

(4). Controls urine volume as consequence of (2).

3. How does tubular secretion/reabsorption occur? Structure of cells lining tubules -- see handout 23A bottom or Sadava fig. 52.13 (51.12) for a different example.

a. Tubules are lined by layer of polarized epithelial cells (similar to those lining intestine)

b. Materials must cross epithelial cells to enter or exit lumen of tubules.

c. Interstitial fluid separates epithelial cells and peritubular capillaries.

d. Epithelial cells have different proteins/channels/transporters on their two surfaces -- the apical or luminal surface (facing lumen) and basolateral surface (facing interstitial fluid and capillaries).

e. Cells in different parts of the tubule have different transporters/channels on their luminal surface.

f. All cells in tubule that absorb Na⁺ have the Na⁺/K⁺ pump on their basolateral surface. Other transporters may vary.

g. What cells transport (& in which direction) depends primarily on which transport proteins are on the luminal surface. Depending on transporters, cells can secrete materials into lumen or reabsorb material from lumen.

h. Cells lining tubule do actual secretion/reabsorption but peritubular capillaries remove reabsorbed material or provide material to be secreted. Therefore (as shown on handout 23A, top left):

(1). Result of tubular reabsorption = net transfer from filtrate to capillary.

(2). Result of tubular secretion = net transfer from capillary to filtrate.

Try problem 12-3.

4. Example of reabsorption -- see 23A upper right. (Fig. 14-18). How Na⁺ is reabsorbed.

Q: How could K⁺ be secreted? What would you have to add/remove from the diagram?

5 Role of Hormones

a. Overall -- Hormones cause water and/or some remaining Na⁺ to be removed (reabsorbed from filtrate) at end of tubule

aldosterone affects Na⁺ reabsorption (& K⁺secretion)

ADH affects water reabsorption

b. Role of aldosterone in Na⁺ reabsorption

(1). Promotes reabsorption of Na⁺

(2). Stimulates virtually all steps of reabsorption -- all steps shown in 23A, upper right.

c. Role/Mech. of action of ADH

(1). Filtrate entering end of tubule is at minimum osmolarity (Osmolarity = concentration of dissolved particles; see below)

(2). ADH (using cAMP) controls insertion of water channels/pores into membranes of cells lining end part of tubule. See Sadava fig. 52.17 (51.15).

Qs: Where are the water channels that are regulated by ADH?

Are they in the luminal membrane, BL membrane, or both?

Are they inserted or removed in response to hormone?

Why are cells in only some areas of tubule responsive to ADH (or aldosterone)?

(3). Water flows out water channels (if in membrane) because of salt gradient in interstitial fluid surrounding tubule

(4). Diabetes insipidus -- result of no ADH or no response to ADH

d. Questions to think about: Where are the receptors for ADH? Aldosterone? Which hormone elicits a faster response?

See problems 12-8 to 12-10. (See below for location of cells affected by each hormone.)

III. Kidney Structure

A. Overall structure -- see handout 23B or Sadava fig. 52.9 (51.9). Alternatively, see Kimball's biology pages.

1. Kidney has medulla (inner part) and cortex (outer)

2. Functional unit = nephron Sadava fig. 52.7 (51.7 )

3. Visible unit (in medulla) = Renal Pyramid = bottoms of many nephrons

4. Tops of nephrons in cortex

B. Structure of Nephron -- see handout 23B or Sadava figs. 52.7 & 52.9 (51.7 & 51.9) . For EM pictures see Sadava fig. 52.8 (51.8). We may do the parts as we need them, but all are summarized here.

1. Nephron itself -- parts in cortex

a. Bowman's capsule
b. proximal (convoluted) tubule
c. distal (convoluted) tubule

2. In medulla

a. Loop of Henle
b. Collecting duct (shared by many nephrons)

3. Capillaries

a. 2 sets in series

(1). Glomerular
    (a). form glomerulus inside Bowman's capsule
    (b). function in filtration

(2). Peritubular
    (a). surround tubules
    (b). fyi: part in medulla (surrounding loop of Henle) is called the vasa recta
    (c). function in secretion & reabsorption

b. How capillaries connected. Circulation goes as follows:

Artery (from heart) → afferent arteriole → glomerular capillaries → efferent arteriole → peritubular capillaries → venule → vein (back to heart)

IV. Kidney Function, revisited.

A. Function of Nephron -- Let's follow some liquid through.

1. Filtration in glomerulus

2. Reabsorption & secretion (of most substances) occurs in proximal tubule

3. Loop of Henley -- overall picture of state of filtrate

a. Definition: Osmolarity (Osm) = total solute concentration = concentration of dissolved particles = osmol/liter. (One osmol = 1 mole of solute particles.)

Examples: 1M solution of glucose = 1 Osm; 1M solution of NaCl = 2 Osm.

b. Events in Loop

(1). Descending: Water goes out -- Osmolarity increases as filtrate descends due to loss of water

(2). Ascending: Na⁺ goes out -- Osmolarity decreases as filtrate ascends due to loss of salt; reaches min. value less than that of blood. Therefore can excrete urine that is hypo-osmotic (less concentrated) than blood.

(3). Overall: Net effect of going through countercurrent loop -- less volume, less total salt to excrete (even if filtrate and blood are iso-osmotic when done).

4. Distal Tubule & Collecting Ducts

a. Control of removal from filtrate (reabsorption) of remaining Na⁺ (Role of aldosterone.)

b. Volume Control -- occurs in collecting ducts. (Role of ADH.)

B. Details for Proximal Tubule

1. Many substances removed from lumen by secondary act. transport

a. examples: glucose and amino acids

b. AA etc. cross apical/luminal surface of epithelial cell by Na⁺ co-transport -- therefore a lot of Na⁺ removed from filtrate (along with glucose, AA, etc.)

c. AA etc. exit basolateral side of cells into intersit. fluid by facilitated diffusion

c. Process is similar to absorption in cells lining intestine

2. Na+/K+ pump on basolateral side keeps internal Na+ low.

3. Water follows salt.

4. Secretion of most materials (except K⁺) occurs here -- toxins etc. transported to filtrate

C. Details of Transport Events in Loop of Henley See Sadava fig. 52.10 (51.10)

1. Water permeability. Luminal cell membranes in descending loop and lower part of ascending loop are permeable to water.

2. Generating the Na⁺ gradient in the medulla -- multiplier effect.

a. Luminal cell membranes in rest of ascending are impermeable to water and pump NaCl from lumen to interstitial fluid.

b. NaCl pumped out from ascending loop accumulates in medulla, forming a gradient of increasing osmolarity (outside the tubule) as reach bottom of loop = core of medulla.

c. As NaCl gradient builds up in medulla, more water is pulled out in the descending loop.

d. As more water removed, [NaCl] in tubule builds up, and more is pumped out in step b.

3. Water loss: Filtrate from proximal tubule loses water as it descends into medulla → NaCl stays in tubule → high concentration NaCl in tubule→ to be removed in ascending. (Na⁺ not pumped out of these cells on BL side.)

4. Escalator Effect: If NaCl diffuses into descending loop, it is carried around and pumped out in ascending = escalator effect.

5. Why called countercurrent? Because flow in two sides of loop is in opposite directions -- physically and with respect to osmolarity.

a. First leg (descending) of loop removes water → higher osmolarity in filtrate as it proceeds (on the way down).

b. Second leg (ascending) removes salt → lower osmolarity in filtrate as it proceeds (on the way up).

c. Net effect is higher osmolarity toward the bottom on both legs.

d. Why doesn't flow in peritubular capillaries (vasa recta) wash out the salt gradient in the medulla? Because capillaries exit out the top of the nephron, carrying a low amount of salt.

See problems 12-1 to 12-3.

D. Distal Tubule and Collecting Ducts -- A few more Details

1. Overall

a. Reminder: Filtrate entering distal tubule is at minimum osmolarity

b. This is the only part of the tubule affected by ADH and aldosterone

    (1). Events in distal convoluted tubule (& first part of coll. ducts) depend on aldosterone

    (2). Events in collecting duct (volume control) depend on ADH

c. Hormones cause water and/or remaining Na⁺ to be removed (reabsorbed from filtrate)

    (1). aldosterone affects Na⁺ reabsorption (& K⁺secretion) -- See handout 23B, top right.

    (2). ADH affects water reabsorption

2. Importance of aldosterone (in water/Na+ balance)

a. Promotes reabsorption of Na⁺; water follows (not necessarily in same part of tubule).

b. Amount of Na⁺ reabsorbed due to aldosterone is small % of total, but adds up; affects blood pressure.

c. Aldosterone promotes K⁺ secretion -- this may be of major importance, but we are focusing on role of hormone in Na⁺ balance.

3. Importance of ADH. Controls water retention in body. Osmolarity of filtrate will increase (and volume decrease) in collecting duct if ADH (vasopressin) present and water removed. (See above for mechanism.)

4. Where do the hormones come from? What triggers their production/release?

a. ADH produced by HT (& released in PP) primarily in response to high osmolarity of blood. See Sadava fig. 52.16 (51.14).

b. Aldosterone produced by adrenal cortex in response to inadequate blood flow through kidney, not primarily in response to ACTH. (Requires renin/angiotensin system. See Sadava fig. 52.15, 9th ed., if you are interested.)

See problems 12-8 to 12-13 & 12-15.

Next Time: Last Official Lecture! Wrap up of kidney & hormones, and the intro to immunology. PM lecture at 6:10, not 5:40.

Reminder: Optional lecture on Cancer & Growth Control on Tues, May 3. Usual times, usual rooms.