Review Sheet 2 for Test #3        Biology 2213             Dr. James Adams

-- Chapter 25; on test 3
     Two Major Functions:
        1. Osmoregulation -- Regulating water volume, ions, and acid-base balance
     2. Excretion of Metabolic (Nitrogenous) Wastes (internally produced)
    Auxiliary Functions:
        1. Release of renin from juxtaglomerular cells of afferent arteriole (regulation of BP)
        2. Release of erythropoietin
        3. Converting vitamin D to it's active form
        4. Gluconeogenesis

Urinary System Anatomy -- refer to your laboratory practical AStructures to Know@ sheet, 
        and remember, as always, you are responsible for knowing the epithelial linings/muscle 
        in the walls of the various organs
    Gross Anatomy
        1. Kidney location, Renal capsule, Fat (Adipose) capsule, Renal fascia
        2. Cortex and Medulla (with renal pyramids/columns), Pelvis (with calyces), renal hilus
        3. Renal Artery and Vein, Interlobar arteries and veins, Arcuate arteries and veins
        4. Ureters, Bladder (with trigone; special tri-layered detrusor muscle), urethra, internal and
            external urethral sphincters
    Microscopic Anatomy -- of the Nephron (Renal Tubule System); >1,000,000 per kidney
        1. Renal Corpuscle = Glomerulus + Glomerular (Bowman=s) Capsule (with podocytes/
            filtration memb)
        2. Proximal/Distal Convoluted Tubules (PCT/DCT) 
        3. Nephron Loop (of Henle)m, with descending/ascending limbs/arms; thin/thick segments
        4. Collecting/Papillary Ducts (form renal pyramids)
        5. Blood flow (a portal system) -- Afferent/efferent arterioles (for glomerulus); peritubular
            capillaries; form vasa recta around Loop of Henle in JM nephrons*
        6. Juxtaglomerular (JG) Apparatus -- involves the JG (granular) cells in afferent arteriole
            and macula densa cells in DCT
    Types of nephrons: Cortical (85%); *Juxtamedullary (15%) with long Nephron Loop --
           only juxtamedullary important for concentrating urine

  Urine Formation -- three processes involved: filtration, tubular reabsorption and secretion.
About one fifth of plasma of the blood is filtered from the glomerulus (125ml/min; 180 L/day; or
        entire plasma volume 60X a day!). Of this, less than 1% (1.5 liters/day) leaves the body as
        urine because you reabsorb the other 99% back into the bloodstream, which requires a LOT
        of energy.  The two kidneys (<1% of entire body mass) use 20-25% of O2 (energy) at rest.

    I. Glomerular Filtration is passive; through the filtration membrane
            Filtration membrane -- fenestrated (glomerular) capillaries, basement membrane, slits
                between podocyte processes
        Small molecules (H20, glucose, amino acids) pass freely; molecules larger than 5 nm do
                not enter filtrate; large proteins keep water in bloodstream.
        Blood Pressure higher in glomerulus than other caps.; generates lots of filtrate. Vascular
            resistance in microcirculation around nephron: two arterioles (afferent & efferent)
            greatly control blood pressure in the glomerulus and peritubular capillaries; efferent
            narrower than afferent which reinforces higher BP in glomerulus than most capillary beds
            in the systemic circulation -- necessary for filtration.
        Need to know concept of Net Filtration Pressure (NFP) and Glomerular Filtration Rate
                (GFR) and their effects on filtrate formation
        NFP ends up being a modest 10 mm Hg
      Controls of GFR:
         1. Intrinsic (autoregulation) -- maintains GFR in face of widely fluctuating systemic BP
            a. Myogenic mechanism -- reduced stretch also stimulates renin release (see below)
            b. Tubuloglomerular feedback mechanism -- involves Juxtaglomerular Apparatus
                Macula densa cells respond to filtrate flow rate/osmotic concentration
                    When flow rate slow/osmotic concentration low, promote vasodilation of afferent
                        arterioles; also sets renin-angiontensin mechanism (see below) into motion
                    When flow rate high/concentration high, promote JG cells of afferent arterioles
                        to generate vasoconstriction
        2. Extrinsic controls -- neural and hormonal
            a.  Sympathetic Nervous System Controls -- overall effects discussed previously, 
                 Extreme stress results in great decline of GFR due to significant constriction of
                    afferent arterioles; directly stimulates JG cells to release renin (see directly below)
            b. Renin-Angiotensin-Aldosterone Mechanism (obviously tied in with other influences)
                Influences systemic BP (and therefore indirectly GFR as well)
                    Remember, angiotensin potent vasoconstrictor -- main thrust is to raise 
                systemic BP
by constriction of systemic arterioles
           Angiotensin has various effects on GFR, besides rise in systemic BP, by stimulating
                release of aldosterone from adrenal cortex, ADH from hypothalamus (increases
                    reabsorption of both NaCl and water; which reduces flow in DCT)
        Take home message: nearly constant NFP and therefore GFR can be maintained even
            as systemic BP varies between 80 and 180 (at rest)

    II. Tubular Reabsorption
     180 liters of filtrate produced daily, 1.5 liters of urine released. Approx. 99% of all 
            filtrate must be reabsorbed from filtrate into peritubular capillary blood. Virtually all
            organics reabsorbed; ions (therefore water) under specific controls.
        You will need to know the following concepts (most of which you=ve already been
            exposed to at an earlier date):  Active transport (mostly of Na+), co-(sym-)transport, 
            passive reabsorption, solvent drag, osmosis using aquaporins
        Transport maximum B each substance that is actively or cotransported can only be
            transported at a rate which is based on the flow rate and number of transport proteins;
            for virtually every substance there is a maximum amount that can be reabsorbed.
            Beyond that point, solutes in the filtrate will be excreted.

        Reabsorption in different parts of the Nephron:
            1. PCT (with microvilli) -- majority of reabsorption from here. All organics, approx 
                    65% of Na+ (and therefore water), and selected portions of other ions.
                Also almost all uric acid and some urea (!)
                Any organics (glucose, amino acids) left in the filtrate past the PCT will be
                    lost in the urine (think of diabetes mellitus and glucose)
            2.  Loops of Henle -- descending limb permeable to water; ascending limb is not
(important for concentrating urine, described below); solute transport not  
                    coupled to osmosis (water does not follow the solutes directly in this case)
              By end of Loop of Henle, 25% more of Na+, 10% of water, 35% of Cl- reabsorbed
            3.  DCT and Collecting Duct -- 25 % of volume, and 10% of salt remain
                    Nearly all of both the water and salt can be reabsorbed as needed
                Permeability to water completely dependent on ADH presence to insert
                    aquaporins (facultative water reabsorption); lack of ADH means little water
                    reabsorption from these regions, and release of dilute urine
                Reabsorption of Na+ (and secretion of K+) dependent on aldosterone release
                Remember also that ANF (or ANP) released from the atria when venous return is 
                    high inhibits aldosterone release, and also increases GFR
                Reabsorption of Ca+2 from DCT dependent on PTH
        [Nice summary diagrams:  pgs. 992 - 998]

    III. Tubular Secretion
     This is the ability to put materials (in some cases replace materials) from peritubular 
            capillary blood into the filtrate in the nephron. This includes uric acid and some urea 
            that was reabsorbed, manipulation of K+ and/or H+, and Cl- and/or HCO3-
            (involved in acid base balance)

Controlling Urine Concentration
    When copious amounts of water drunk, need to release dilute urine
    However, we are terrestrial, and much more frequently we face the need to conserve 
        water (concentrate urine) than get rid of excess water.
    Two nephron parts vital to concentrating urine: Nephron Loops and Collecting Ducts
     Remember salts pumped from ascending limb (which draws some water from 
            descending limb); this makes the tissue of the medulla very salty (high osmotic 
            concentration); in other words, as you descend into the medulla, there is an 
            increasing salt gradient. As fluid passes through the collecting ducts, thereby 
            descending through the medulla, increasing amounts of water can be drawn 
            out (assuming ADH is present). Additionally, the collecting ducts are permeable 
            to urea and some urea diffuses out, adding to the medullary solute concentration 
            gradient. In other words, we retain some urea, which sounds weird, but it helps 
            with the ability to concentrate the urine.
    Renal Clearance: A measure of the amount of substance released compared to the 
        amount of the same substance filtered; gives an idea of the reabsorption/secretion 
        capabilities of the nephrons

Urine Characteristics:
    Color/transparency; odor; pH (varies anywhere from 4 to 8)
    Chemical Composition -- most abundant components: water, urea, sodium in that order
        many other ions
    Any organics in the urine (red blood cells, proteins, etc.) indicate some pathology

Rest of Urinary System on lab "Structures to know" sheet -- Ureters, Bladder, Urethra

Know about expansion capabilities of Bladder, and Micturition (Urination; involving 
    involuntary internal urethral sphincter [at bladder] and voluntary external urethral
    sphincter [at abdominal wall in both sexes])

        Almost entire chapter is review of information from previous chapters; very little new
            information, just put together in a different fashion than previously.

Body Fluids -- Water
    Total body water represents $50% of body mass; most in infants, least in elderly
    Adult males avg. 60%; females 50% (fat is the least hydrated tissue)

Fluid Compartments: (numbers for a 70 kg man)
    1. Intracellular Fluid Compartment (ICF) -- 25 liters
    2. Extracellular Fluid Compartment (ECF) -- 15 liters:
        subdivided into plasma (3 liters) and interstitial fluid (several types: 12 liters)
      Main differences between compartments are the solutes; grouped into electrolytes 
            (ions) and non-electrolytes (includes many organics, such as protein)
        Understand concept of milliequivalents for electrolytes (ionic compounds)

You should also know main solutes in all compartments, and therefore the differences 
between them; for example, the main extracellular cation is . . .? . . . the main intracellular 
anion is . . .? (Figure 26.2, pg. 1014)

Fluid Movements Between Compartments -- SEE Fig. 26.3
    The main concept to remember here is that all compartments will more or less remain
        isotonic to one another; any momentary fluctuation in the solute content in one 
        compartment is offset by osmotic movements of water -- thus, volume of ICF is 
        determined by solute concentration of ECF

    Between plasma & interstitial fluid -- across capillary walls (remember capillary 
    Between interstitial fluid and ICF -- selectively across cell membranes
    Only plasma circulates, so it is the ultimate link in exchanges between compartments

  I.  Water Balance -- Input must equal output; see Fig. 26.4, pg. 1016
        Inputs -- drink, food, cellular respiration (and other metabolic processes)
        Outputs -- urine, sweat, feces, insensible losses (respiratory surfaces, skin)
    Regulation of Intake -- the thirst mechanism
        Involves the hypothalamus -- remember, the BBB is leaky here, so that the 
            hypothalamal receptors can sample the plasma contents; thirst triggered when 
            osmotic content of plasma elevated (water content lower), which causes
            hypothalamal osmoreceptors to lose water, which depolarizes them
        Salivary glands reduce water output -- dry mouth
        Thirst quenched almost immediately -- moistening of upper GI tract mucosae and 
            stretch receptors in stomach involved. Prevents overhydration
    Regulation of Output
        We have obligatory water losses (insensible, fecal and a certain minimal urine loss)
        Renal concentrating mechanisms are the main way to conserve water.  This involves
            release of ADH from the hypothalamus/posterior pituitary at the same time as
            the sensation of thirst is generated
    As you will see, water balance very much tied to Na+ balance as well (where
                solutes go, water follows).
B know about dehydration and hypotonic hydration

  II.  Electrolyte Balance -- will examine Na+, K+, and Ca+2 mainly (though this will 
        involve Cl- and HPO4-2)
A.  Central Role of Na+ -- Most abundant extracellular cation, and only one exerting 
            significant osmotic pressure, which means it is central in moving water around 
            between compartments
          (Don=t forget, Na+ also plays a major role in electrical gradients)
      Regulation of Na+ Balance -- interestingly, virtually no chemoreceptors that respond 
            specifically to Na+ have been found yet in the body
     1.  Aldosterone is, of course, a key player; stimulators of aldosterone release include
            i. Angiotensin
            ii. Elevated K+ levels                 (Addison=s disease/pica)
         3.  Other Hormones -- Female Sex Hormones
         4.  Baroreceptors in the Circulatory System -- in essence, these are Na+ receptors, 
                since blood volume is dependent on solute volume
     Remember, besides pulling water around, Na+ typically also pulls Cl- around

    B.  Potassium Balance -- very much tied to acid base balance, as shifts in 
            H+ often offset by opposite direction shifts in K+. With acidosis, ECF K+ goes up; 
                with alkalosis, K+ re-enters cells (H+ exits)
            You should know the reasons why this happens! (See acid-base balance below)
        Regulation of K+ Balance -- main site:  DCT and cortical collecting ducts
            Main thrust of renal mechanisms is to excrete K; faced with shortages the kidneys 
                have a very limited ability to conserve K+, and K+ may be lost even when needed.
            Factors involved: K+ levels directly; aldosterone

    CCalcium (and Phosphate) Balance -- 99% of body=s calcium is in bones (as calcium
            phosphate salts), yet ionic calcium necessary for many physiological events
        Regulation of Ca+2 Balance -- two hormones, PTH and calcitonin, of which PTH is far 
                more crucial (you already know what these hormones do!)
            Calcitonin (from thyroid) targets mainly bones (osteoblasts)
            PTH targets: bones (osteoclasts), small intestine (vitamin D) and kidneys (reabsorp. 
                from DCT, conversion of inactive to active vitamin D)    

            Osteoclasts/-blasts working on bones will also release/deposit phosphate ions from/to
                bones, so PTH and calcitonin are majorly involved in phosphate balance as well
            As a rule, 75% of filtered phosphate ions reabsorbed (regulated by its transport

    D.  Regulation of Anions -- know about Cl- and HPO4-2 (phosphate); be aware that, 
        like potassium, chloride ions are also involved in acid-base balance by being shifted 
        with bicarbonate (HCO3-)

  III.  Acid-Base Balance -- pH balance so crucial to normal metabolic functioning
            ICF typically at pH 7; plasma varies but typically slightly alkaline
            Most H+ generated as metabolic by-products
    Regulation of H+ Balance: three main mechanisms
        1. Chemical Buffer Systems -- involves weak acids and associated weak bases
            a. Bicarbonate Buffer System -- the only important ECF buffer system (though there 
                is some protein buffering in plasma
            b. Phosphate Buffer System -- only important in ICF, though protein buffering also 
                important in ICF
            c. Protein Buffer Systems -- amine (base) and carboxyl (acid) ends; also important 
                in ICF
        2. Respiratory Regulation -- two times buffering capabilities of all chemical buffers
            Clearly, this is directly tied to the bicarbonate buffering system
         Changes in AVR in a healthy individual can go well beyond compensating for most 
                pH fluctuations
        3. Renal Regulation -- only kidneys can actually remove metabolically produced acids
            Mainly this involves regulating bicarbonate ion levels (conserving and generating new
                ones; understand concept presented in Fig. 26.13, pg. 1030)