• Some functions of the kidneys:

• Maintain water balance

• Regulate electrolyte (ion) concentrations

• Maintain proper plasma volume for long term regulation of blood pressure

• Maintain proper acid-base balance (pH) of plasma

• Excretion of wastes and foreign substances

• Secrete the hormone erythropoietin and the enzyme renin, and convert vitamin D₃ from the skin into its active form

• Kidneys

• Paired, bean-shaped organs about the size of a fist.

• Receive 20-25% of the cardiac output.

• Has an outer cortex and an inner medulla.

• The functional unit of the kidneys is the nephron.

• Each nephron has a vascular and tubular component.

• Key vascular components:

• Afferent arterioles - Carry blood to the glomerulus

• Glomeruli - Capillaries which filter plasma

• Efferent arterioles - Carry blood away from the glomerulus

• Peritubular capillaries - Supply renal tissue w/ blood

• Key tubular components:

• Bowman's capsule - Collects glomerular filtrate.

• Proximal convoluted tubule, Loop of Henle (descending and ascending limbs), Distal convoluted tubule, Collecting duct

• Renal corpuscle = Bowman's capsule + glomerulus

• 2 types of nephrons (See page 564, Fig. 17.6)

• Cortical

• More numerous, glomeruli lie in outer cortex, have short loops of Henle that barely dip into the medulla

• Juxtamedullary

• Less numerous, glomeruli lie in inner cortex, have long loops of Henle that plunge deep into the medulla, vascular system has hairpin loops called the vasa recta

• 3 basic processes are involved in the formation of urine:

• Glomerular filtration - Filtration of a protein-free plasma from the glomerulus into Bowman's capsule. (Referred to as an ultrafiltrate once in Bowman's capsule.)

• Tubular reabsorption - Selective movement of filtered substances from the tubule into the capillaries.

• Tubular secretion - Selective movement of non-filtered substances from the capillaries into the tubule.

• Excretion - Elimination of substances from the body in the urine. It is the result of the first 3 processes.

• Do not confuse secretion with excretion.

• See page 577 (Fig. 17.22) for a diagram of above processes.

• Glomerular filtration - Initial stage of urine formation.  Only about 20% of the plasma entering a glomerulus is filtered.

• Process depends on several factors:

• Glomerular Capillary Blood Pressure (GCBP) - (Favors filtration)

• Plasma Colloid Osmotic Pressure (PCOP) - (Opposes filtration)

• Bowman’s Capsule Hydrostatic Pressure (BCHP) - (Opposes filtration)

• Net filtration pressure (NFP) - Net difference favoring filtration.

• NFP = GCBP - (PCOP + BCHP)

• NFP = 55 mm Hg - (30 + 15) mm Hg = 10 mm Hg

• NFP favors filtration if value > 0 and opposes filtration if value < 0.

• Permeable nature of glomerular capillaries contributes to glomerular filtration. The glomerular capillaries are about 100X more permeable than the systemic capillaries because walls contain numerous pores.

• Glomerular filtration rate (GFR) - Volume of filtrate formed by both kidneys each minute.

• Rate of glomerular filtration is about 115-125 ml/min, or about 160-180 L/day. Unless most of this is reabsorbed into the bloodstream, the body would quickly dehydrate.

Regulation of GFR

• Extrinsic control of GFR occurs through the sympathetic N.S. control of vasoconstriction of afferent arterioles and a subsequent decrease in blood flow.  This decreases GFR and, therefore, diverts blood flow elsewhere.

• Renal autoregulation - Intrinsic regulatory changes designed to maintain a relatively constant GFR in the face of fluctuating blood pressures. One way in which it occurs is via locally produced chemicals that affect the afferent arterioles.

• If GFR increases:

• Vasoconstriction Blood flow into glomerulus   Glom. Cap. B.P. Net filtration P GFR

• If GFR decreases:

• Vasodilation   Blood flow into glomerulus   Glom. Cap. B.P. Net filtration P GFR

Tubular Reabsorption

• Proximal tubule (PT) initiates the process of concentrating the ultrafiltrate.

• About 65% of salt and water is reabsorbed before it can reach the loop of Henle.
• Other substances reabsorbed include: glucose, bicarbonate, amino acids, and urea (waste product of protein metabolism).

• Descending limb of Loop of Henle

• Highly permeable to water.

• Thin segment of ascending limb of Loop of Henle

• Passive transport of NaCl and urea.

• Thick segment of ascending limb of Loop of Henle

• Active transport of Na⁺, passive transport of Cl^-.

• Distal tubule

• Secretes K⁺, H⁺, and ammonia (NH₃) into the tubule.
• Transports Na⁺, Cl^-, and HCO_3- out of the tubule.

• Collecting duct

• Passive transport of water (ADH influenced) and urea.

Countercurrent Multiplier System

• The ability to excrete urine of varying concentrations depends on the countercurrent multiplier system and ADH.
• Components of countercurrent multiplier system:

• Loops of Henle of juxtamedullary nephrons establish vertical osmotic gradient (VOG.)
• Vasa recta prevent loss of the VOG by maintaining hypertonicity of renal medulla by countercurrent exchange (passive exchange of solutes and water between the two limbs of the vasa recta and ISF.)
• Collecting ducts - Use gradient (along with ADH) to produce urine of varying concentrations.

• VOG is maintained in the ISF of medulla of each kidney and increases from the cortical boundary to the depths of the medulla.
• Presence of the large VOG enables the kidneys to produce urine that ranges in concentration from ~ 100-1400 milliosmolar (mOsm).
• Countercurrent multiplication - Process by which the descending and ascending limbs interact to produce a concentrated interstitial fluid (ISF) in the renal medulla.

• Why concentrate the fluid in the descending limb, only to dilute it in the ascending limb?

• Doing so creates the VOG.
• It ensures that a hypotonic fluid will enter the distal tubule and ultimately enable the kidneys to excrete a concentrated urine.

• Medullary VOG permits excretion of urine of differing concentrations by means of ADH-controlled, variable water reabsorption from the final tubular segments.
• The kidney's ability to concentrate urine and to minimize water loss is possible only because of the presence of the medullary VOG.
• If there wasn't a VOG, then a urine no more concentrated than the body fluids could be produced.

• Urea recycling contributes to medullary ISF hypertonicity.

• Thin ascending limb of L of H and the lower collecting duct (CD) are permeable to urea.
• Urea can diffuse down its concentration gradient from CD to ascending limb.

• Antidiuretic hormone (ADH; Vasopressin)

+ water reabsorption by increasing the permeability of the collecting duct to water after insertion of water channels (aquaporins) in the membrane. The CD is relatively impermeable in the absence of the channels.

Response of the CD to ADH is graded; as ADH increases, more water channels are inserted into the membrane and the permeability to water increases.

ADH is inhibited in response to alcohol and an excess fluid intake.

• Glucose and amino acids are completely reabsorbed by sodium-dependent secondary active transport and exhibit a transport (tubular) maximum.
• Unwanted waste products are not reabsorbed.

• Secretion

• Serves to hasten the elimination of substances (including potentially dangerous substances) in the urine.
• Some important substances secreted into the tubules are K⁺, H⁺, and ammonia (NH₃).

• Sodium transport is not under hormonal control in the proximal tubule.

• Hormonal control of sodium reabsorption occurs in the late distal tubule (some) and cortical collecting duct (most).  ~ 8-10% of filtered Na⁺ is dependent upon hormones.

• Occurs via the Renin-Angiotensin-Aldosterone system (R-A-A system) in response to decreased NaCl, decreased fluid volume, or decreased MAP.

• Sensors are located in the juxtaglomerular apparatus (JGA) = granular cells (located within afferent arteriole and secrete renin) + macula densa (located in walls of distal tubule)

	Renin (kidney)		ACE (lungs)		+
Angiotensinogen (liver)		Angiotensin I (AI)		Angiotensin II (AII)		Aldosterone

• AII stimulates ADH, thirst to increase fluid intake, and arteriolar vasoconstriction.

• Aldosterone

• Stimulates Na⁺ reabsorption and stimulates K⁺ and H⁺ secretion.

• Stimulated directly by increased blood K⁺ (hyperkalemia) and indirectly by decreased blood Na⁺ (hyponatremia.)

• Atrial natriuretic peptide

+ sodium and water excretion (or inhibits reabsorption).  Inhibits R-A-A system.

+ by increased fluid volume, NaCl, and MAP.  These are opposite to the factors which stimulate the R-A-A system.

 

• (refers to the regulation of free [H⁺] in body fluids)

• Acids - Substances that release H⁺ when in solution.
• Bases - Substances that accept H⁺ when in solution.
• pH - Measure of the hydrogen ion concentration in a solution.
• Concentration of hydrogen ions and pH are inversely related.
• Every unit change of pH represents a 10-fold change (increase or decrease) in hydrogen ions.
• Acidic (pH < 7) vs neutral (pH = 7) vs basic (pH > 7) solutions.
• Acidosis vs alkalosis
• Blood pH is regulated at ~ 7.4 to prevent profound effects on the chemistry of the body.
• Hydrogen ions are continually being added to body fluids as a result of metabolic activities.
• 3 ways to resist changes in hydrogen ion concentration:

• Buffers - Molecules that act to minimize pH changes.
• Respiratory control of pH
• Renal control of pH

• Examples of buffers: HCO₃^-(plasma buffer), proteins and hemoglobin (intracellular buffers), phosphate and ammonia (urinary buffers).
• In the urine, H⁺ binds with NH₃ (secreted by tubule) to form an ammonium (NH₄⁺) ion. NH₄⁺ cannot be reabsorbed by tubule.
• Kidneys regulate blood pH by adjusting:

• Hydrogen ion excretion
• Bicarbonate reabsorption and excretion

Renal Acid-Base Imbalances   (May also want to see pgs. 545-546 in Chap. 16)

• Metabolic acidosis - Acidosis characterized by a reduction in plasma bicarbonate or an increase in hydrogen ions.

• Can be caused by:

• Diarrhea, increased fatty acids, exercise-generated lactic acid production, ketone bodies from uncontrolled diabetes

• Metabolic alkalosis - Alkalosis characterized by an increase in plasma bicarbonate or a decrease in hydrogen ions.

• Can be caused by:

• Vomiting, ingestion of alkaline substances (NaHCO₃)

                                                   Other Urinary Anatomy

• Ureter

• Carries urine from kidney to bladder

• Bladder

• Temporarily stores urine.

• Capable of tremendous expansion.

• Parasympathetic nervous system stimulates bladder contraction.

• Exit of urine from bladder is guarded by 2 sphincters (one smooth muscle and one skeletal muscle.)

• Micturition = urination

• Micturition is under reflex control from the sacral spinal cord; there is also voluntary control.

• Incontinence - Inability to prevent urine discharge.

• Urethra

• Carries urine from bladder to the outside.

• Shorter in females (4 cm) than in males (20 cm.)

• In males, passes through the prostate and penis; provides a route for discharge of urine and semen