C2006/F2402 '06 Outline for Lecture 21 --  (c) 2006 D. Mowshowitz  -- Lecture updated 04/17/06

Handouts 21A to 21 D.  21A = Muscle AP's; 21B = Heart Structure & Circulation 21C = Overall Kidney structure; 21 D = Structure/Function of Kidney Tubule.
Note: Details of Excitation-Contraction coupling in muscle are in Lecture 22 of '05. Discussion of Gas Exchange in is Lecture 23 of '05. These topics will not be covered in lecture and you are not responsible for them. Links are included if you are curious or studying for MCATs.

I. Heart Structure/function

    A. Two Types of cardiac muscle cells

1. Contractile cells

a. Bridge cycle etc. much like skeletal.

b. FYI: Similar to oxidative/slow twitch skeletal (see notes of last time) -- low fatigue rate but very oxygen dependent.

c. Cells are coupled electrically (gap junctions at intercalated disks)

d. Special features of AP in membrane (see handout 21-A)

(1). AP lasts much longer (as long as contraction) so tetany is impossible. Each contraction ends before next AP arrives. (see fig. 14-15 on handout & 47.7  & 49.8 (47.11) of Purves)

(2). Prolonged AP (long depolarized phase) is due to delay in opening slow voltage gated K+ gates and opening of Ca++ channels. (see fig. 14-14 on handout & 49.8 in Purves.)

e. Role of Pacemakers.

(1). Trigger for contraction is signal from pacemaker cells of heart, not from AP of nerve.

(2). Contractile cells do not have pacemaker activity.

2. Pacemaker cells -- see handout 20-C or 21A (fig. 14-16) or Purves 49.6 (49.7). These largely discussed last time.

a. Have pacemaker activity -- Fire spontaneously

b. Mechanism of pacemaker activity: Depolarize slowly to threshold pacemaker potential AP when reaches threshold. (See notes of last time.)

c. Set pace of heart beat -- Autonomic neurons release transmitters that slow or speed up pace; see last time.

d. Special Features of AP -- AP (spike in potential) in pacemaker cells is largely due to inrush of Ca++ not  Na+.  (see fig. 14-6, panel (c) on handout 20C). When cells depolarize to threshold, voltage gated Ca++ channels, not voltage gated  Na+ channels, are opened.

3. What accounts for differences in function between the two types of cardiac cells? Have different channels. Look at handouts to see how differences in electrical properties correlate with differences in channels, ion flows, etc.

See Problems 11-1 & 11-2.

    B. Structure of heart --  Where are the contractile and pacemaker cells? See handout 21B, Purves Fig. 49.3 (49.4)

1. Orientation: Note all pictures of heart show person facing you, so "right" 1/2 of heart is on left of picture.

2. Structure: "Subway diagram" on top of handout shows what is connected to what, but no real anatomy.

3. Anatomy: Pictures in middle of handout show approximations of actual structures.

    C. Position, function of pacemaker cells (nodes), bundle of His, Purkinje fibers  -- see Purves fig. 49.7 (49.8) & handout middle right.

1. All these cells have pacemaker activity -- make up the conduction system -- carry the AP to all parts of the heart. Note these cells are muscle, not nerve.

2. SA node usually in charge. SA node has the fastest firing rhythm -- normally controls heart beat. Fires first.

3. Role of AP in SA node. Causes atria to contract, pushing blood into ventricles. Causes AV node to fire after a short delay

4. AP in AV node spreads to bundle of His and Purkinje fibers

5. Bundle of His etc. causes ventricles to contract, from bottom up, pushing blood out top of heart. 

    D. Overall view of circulation  -- see handout 21B and Purves p. 945 (870).

1. There are 2 loops of circulation -- to lungs (pulmonary) and to body (systemic) -- see picture on bottom of handout. Different blood vessels go in parallel to various parts of body. (Helps to compare all pictures on 21B to understand the structure of heart and circulation.)

2. Arteries go away from the heart; don't necessarily carry oxygenated blood

3. Structure: Arteries and veins, arterioles and venules are surrounded by smooth muscle; capillaries are not.

4. Cardiac cycle -- systole & diastole

a. Systole -- ventricles contract ("squeeze"), blood pumped out to system

b. Diastole -- ventricles relax; fill with blood

c. Note: the terms systole (contraction) and diastole (relaxation) can be used to refer to the state of the ventricles or to the state of the atria. In common usage, the terms always refer to the state of the ventricles. 

See problems 11-3 to 11-6.

II. Kidney Structure & Function (Handouts 21C & D). See also Purves Ch 51.

    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 and what will be retained.

2. What processes occur in kidney? Carries out filtration, tubular secretion, & tubular reabsorption ,& then controls volume. See handout 21D or Purves 51.7.

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. Therefore 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. Therefore filtrate does NOT carry certain materials (which are selectively reabsorbed) -- conserves valuable materials; returns them to circulation.

d.  Volume: Water loss is adjusted later using ADH. Therefore urine can be more (or less) concentrated than the plasma -- can vary concentration and/or volume to suit need. Water loss/conservation controls volume of body fluids -- plasma, extra cellular fluid, etc. (& blood pressure)   

3. How does Tubular secretion/reabsorption Occur? Structure of cells lining tubules  -- see handout  21D or Purves fig. 51.12, for an example

a. Tubules 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 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 tubule have different transporters/channels on luminal surface.

f. Cells in different parts of tubule all have the Na+/K+ pump on their basolateral surface. Other transporters may vary.

g. Depending primarily on which transport proteins are on luminal surface, cells secrete materials into lumen or reabsorb material from lumen.

h. Cells lining tubule do actual secretion/reabsorption but capillaries remove reabsorbed material or provide material to be secreted. Therefore (as shown on 21D, top left):

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

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

i. For an example of reabsorption -- see 21D, upper right. (Fig. 14-18).

Try problem 12-3.

    B. Overall structure -- see handout 21C or Purves fig. 51.9

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

2. Functional unit = nephron (Purves 51.7 )

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

4. Tops of nephrons in cortex

    C. Structure of Nephron -- see handouts or Purves fig. 51.7  & 51.9 . For EM pictures see Purves 51.8.

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 = filtration

(2). Peritubular
    (a). surround tubules
    (b). vasa recta = part in medulla (surrounds loop of Henle)
    (c). function in secretion (concentration of substances in filtrate) & reabsorption (removal of substances from filtrate)

b. How capillaries connected

Afferent arteriole glomerular capillaries efferent arteriole peritubular capillaries venule

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

1. Filtration in glomerulus

See problem 12-6.

2. Reabsorption in proximal tubule

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

(1). examples: glucose and amino acids

(2). Cross apical/luminal surface of epithelial cell by Na+ cotransport

(3). Exit basolateral side of cells into intersit. fluid by facilitated diffusion

(4). Process is similar to absorption in cells lining intestine

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

c. Water follows salt.

3. Events in Loop of Henley and rest of tubules -- 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.) A 1M solution of  glucose  = 1 Osm; A 1M solution of  NaCl = 2 Osm. 

b. Events in Loop

(1). Osmolarity increases as filtrate descends due to loss of water

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

c. Events in distal convoluted tubule (& first part of coll. ducts) depend on aldosterone -- ald. promotes reabsorption of Na+ and water follows. (See handout 21D, top right.)

d. Events in collecting duct depend on ADH -- Osmolarity will increase (and volume decrease) in collecting duct if ADH (vasopressin) present and water removed

4. Details of Loop of Henley (See Purves 51.10)

a. Cells in descending loop and lower part of ascending loop are permeable to water

b. Cells in rest of ascending are impermeable to water and pump NaCl from lumen to interstitial fluid.

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

d. Filtrate from proximal tubule loses water as it descends into medulla high concentration NaCl in tubule to be removed in ascending

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

f. Why called countercurrent? Because flow in two sides of loop is in opposite directions  physically and with respect to osmolarity. First leg (descending) of loop removes water higher osmolarity in filtrate; second leg (ascending) removes salt lower osmolarity in filtrate.

See problems 12-1 & 12-2.

5. Distal Tubule and Collecting Ducts

a. Filtrate entering here is at minimum osmolarity

b. More water and/or Na+ removed under influence of aldosterone and ADH

c. Role/Mech. of action of ADH

(1). ADH (using cAMP) stimulates insertion of water channels/pores into membranes of collecting duct (and maybe late distal tubule)

(2). Water flows out ADH-stimulated channels (if in membrane) because of salt gradient in medulla.

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

d. Role of aldosterone

(1). Promotes reabsorption of Na+; water follows.

(2). Amount of Na+ reabsorbed due to aldosterone is small % of total, but adds up.

See problems 12-9, 12- 11 & 12-15.

III. Regulation of kidney function 

    A. Regulation of release of ADH from post. pituitary (See Purves 51.14 [51.15])

1. Sensors -- 2 types, since regulating two different variables

a. Stretch receptors in arteries (sensors for blood volume) -- this comes into play only if large volume change

b. Osmo-receptors in HT (sensors for solute levels in blood) -- this is the primary sensor

2. Response: ADH release up if osmolarity of blood up or stretch receptors (way) down

3. Thirst: ADH release & thirst both triggered by same receptors.

4. Feedback Loop: ADH release (& thirst up) water intake up, water loss down in kidney, & constriction of arterioles in extremities restore blood volume, reduce osmolarity (and restore blood pressure)

4. Speed: Effects of ADH are relatively fast -- no prot. synthesis required. (Effect on water loss takes a while, since ADH affects formation of new urine, not state of pre-existing urine.)

    B. Autoregulation by kidney -- flow through kidney (GFR) must be adequate to keep kidneys functioning properly. Flow is adjusted through local effects and overall control of blood pressure.

1. GFR Adjustments -- dilate/constrict afferent arteriole

Low BP (low flow through kidney)  dilation of afferent arteriole (to glomerulus) increases flow through kidney increase in GFR (glomerular filtration rate). High BP has opposite effect.

See problem 12-4.

2. Renin/Angiotensin/Aldosterone System

a. Low BP or GFR in Kidney kidney secretes renin

b. Renin catalyzes rate limiting state in conversion of angiotensin precursor (in blood) angiotensin II (active)

c. Effects of Angiotensin II

(1). Acts on adrenal cortex aldosterone Na+ reabsorbed in kidney and elsewhere

(2). Acts directly to raise BP -- is vasoconstrictor. (Also stimulates thirst & release of ADH)

(3). Note that effects of aldosterone are slower than others as they involve steroid protein synthesis

See problem 12-8.  By now you should be able to do all of problem set 12 except 12-5. (For 12-5 & 12-14, consider the max. osmolarity of urine. It's 1200 mOsm -- less than sea water.)

IV. Regulation of Blood Pressure.

Multiple sensors, effectors, and feedback loops are involved in control of both contents of blood and pressure/volume. Many have already been discussed. Major circuit (in addition to those already discussed ) -- uses PS/S system to adjust heart rate & constriction/dilation of arterioles in response to sensors (primarily) for arterial BP. IC = cardiovascular control center in brain stem (medulla);  integrates information from arterial sensors and from other parts of brain. Additional details are in the texts and/or notes of 2004.