C2006/F2402 '04 -- Outline for Lecture 23

(c) 2004 Deborah Mowshowitz . Last updated 04/22/2004 03:59 PM

Handouts: You need 22-C from last time; 23A & 23B (Table at end of this lecture + types of blood cells).

I. Kidney Function, cont. (See notes of Lecture 22 & handout 22-C)

• Structure of cells lining tubule
• Reabsorption in proximal tubule
• Details of events in Loop of Henle
• Distal Tubule & Collecting Ducts -- roles of ADH & aldosterone

See problems 12-9 & 12-15.

II. Regulation of kidney function & Blood Pressure (BP)

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 --> higher blood pressure, more dilute blood

4. Speed: This is fast -- no prot. synthesis required

1. GFR Adjustments -- dilate/constrict afferent arteriole

Low BP --> 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

Question to consider: What is the correlation between total body salt and blood pressure (or volume)? Is it the same as the correlation between osmolarity and blood pressure? In other words, if total body sodium is low, or osmolarity is low, what do you expect of the corresponding blood volume? Normal, low or high?

(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.)

III. Summary of regulation of blood pressure (see  handout 23A. & Purves figs. 49.19 & 49.20 [46.20 & 46.21] )

1. Major circuit that controls BP

a. IC = cardiovascular control center in medulla (Purves 49.20 [46.21])

b. sensors = stretch receptors (= baroreceptors) in major arteries

c. effectors = heart, peripheral blood vessels (constrict/relax)

d. circuits -- uses PS and S.

See problems 11-10 & 11-16.

2. IC has other inputs and outputs

a. Additional input from

(1). chemoreceptors in arteries (for oxygen)

(2). chemo- and baro- receptors in higher brain

b. Additional output -- to adrenal medulla through sympathetic system   (--> epinephrine)

3. Other effectors/sensors operate independently of IC (Purves 49.19 [46.20])

a. HT controls production of ADH/vasopressin & thirst -- system effects vasoconstriction, water intake & conservation.

b. Renin/angiotensin/aldosterone system controlled by kidney GFR (& other inputs) -- systemic effects on thirst, vasoconstriction and salt (therefore water) retention

c. These factors affect both blood volume and capacitance of blood vessels

1. Heart beat rate and strength of contraction -- controlled by PS (- effect), E, S (+ effect)

2. Constriction/dilation of arterioles (contraction of smooth muscle) -- mostly contract in response to S (working on alpha receptors) and hormones (ADH, angiotensin, E)

3. Water retention and intake -- affected by

a. aldosterone (promotes water and salt retention)

b. angiotensin (affects thirst & ADH release)

c. ADH (affects water retention)

    C. Multiple Regulated variables

1. Contents of blood -- primarily osmolarity and oxygen (CO₂ levels largely regulated through breathing)

2. Actual pressure of blood -- monitored systemically (in arteries, HT) and locally (in kidney) to maintain homeostasis of both overall level and level in kidney

    D. Multiple Systemic Sensors

1. Osmoreceptors in HT

2. Baroreceptors (measure pressure through stretch) & chemosensors (for O₂) in arteries

    E. Multiple Local sensors & effects already discussed -- how they can lead to systemic effects

1. Capillary beds in tissues -- Autoregulation of flow through capillary beds in response to levels of CO₂ and O₂ levels -- too much dilation can --> low systemic blood pressure (BP). See Purves 49.18 [46.19].

2. Temperature: Dilation of blood vessels in order to maintain temperature homeostasis --> low BP

3. Kidney -- changes in GFR (to adjust blood flow through kidney) can trigger not only local changes but also systemic effects through release of ADH, aldosterone, & angiotensin as discussed above.

See problem 11-13.

IV. Specific (= Acquired) Immune Response -- Major cells and parts Features??

    A. Intro. What are major proteins of the specific immune system? 

1. Antibodies. Already discussed antibodies as chemical reagents. What are antibodies really needed for physiologically? To combat infection and maybe to prevent cancer.  (Details on antibody structure will be covered later.)

2. What other proteins are involved? 

a. Immune system uses 3 types of proteins that have a common evolutionary origin and certain features in common. These are antibodies, TCR and MHC. Roles & structures will be explained below.  For pictures see Purves 19.11[18.12] for antibodies & Purves 19.14 [18.16] for TCR.

b. All 3 types of proteins have a "constant" part and a "variable part." Constant part determines where protein is (cell surface? What kind of cell? etc.) and its general function. Variable part determines what antigen/epitope will bind to the protein.

    B. What are the Important Features to explain? (This will be covered next time.)

1. Specificity & Diversity -- each Ab or TCR is directed against one epitope or antigenic determinant (= piece of antigen -- see Purves 19.6 [18.7]), and there are many, many different antigens. How can you make so many different Ab's or TCR's, each specific for a particular antigen or piece of it?

2. Memory -- secondary response is faster, larger, better than primary response. In secondary response, make more Ab, Ab is more effective (binds better to Ag because of slight changes in amino acid sequence of Ab), and Ab response lasts longer. (Purves 19.8 [18.9]) How is this done?

3. Tolerance -- can distinguish self/nonself or normal/abnormal -- make Ab only to foreign/abnormal stuff (except in disease states).  . How does this work?

4. Response is adaptable -- response depends on amount and type of antigen. How do you "know" which antibody to make in response to a particular antigen?

    C. Specific Immune system has 2 branches

1. Humoral response -- binding and destruction of antigen done by proteins in "humors" = antibodies in blood and secretions (for ex. milk, tears).

2. Cellular or cell-mediated response -- binding and destruction of antigen done by whole cells bearing a TCR.

    D. What Cells are involved?  White blood cells (leukocytes) -- contain no hemoglobin. WBC divided into two main types

1. Phagocytes -- macrophages, dendritic cells, etc. ( See Purves 19.2 [Table 18.1]). Involved in processing antigens as will be explained. 

2. Lymphocytes. Found in lymph nodes and elsewhere. Do actual production of antibodies and/or execution of cellular immune response. Divided into B and T cells.

a. Action of B cells is to make antibodies. Major players in humoral response.

B cells --> release antibody --> Ab (antibody) binds Ag (antigen -- usually on surface of microbe) --> trigger destruction of microbes (microbes are engulfed by phagocytes or lysed) often with the help of complement . (See Purves 19.12 [18.14]) Allergies are a side effect of this system.

b. Action of  (cytotoxic) T cells is to use a TCR on their surface to bind to abnormal cells; use other proteins to destroy the abnormal cells. Major players in cell-mediated response.

T cells --> Use TCR to bind to Ag on surface of virus infected eukaryotic cell --> destroy cell by triggering of apoptosis. T cells use proteins called perforins to make holes in and help kill targets (with the assistance of other proteins). Note complement is similar but works on prokaryotic invaders; perforins work on rogue eukaryotic cells. (See Purves 19.15 [18.17]) This is why grafts fail; foreign cells of graft look like infected (defective?) cells and are destroyed. 

    E. Major features of 2 branches of specific immune system

Notes: 
*T cell receptor is NOT the receptor for T cells -- it is the protein on the T cells that is the receptor for an antigen. It is the receptor of T cells, not the receptor for T cells. (By analogy, antibody attached to B cells is sometimes called "the B cell receptor" or BCR instead of antibody. BCR and TCR both act as receptors for antigen -- they allow antigen to trigger the immune response, as explained below. So they are also referred to as B or T cell receptors for antigen.)

** Complement = a series of proteins found in blood. Activation of complement involves a cascade of activations similar to that involved in blood clotting. Complement binds to antibody-antigen complexes attached to microbes and triggers phagocytosis or lysis of the microbe bearing the complex. (See Purves 19.3 [18.4])

Next Time: More on the Immune System.