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The Kidney & It’s Function

I. Introduction
   A. Vertebrate Physiology Reflects Their Origin in an Aquatic Environment
   B. Body Water Must Be Regulated to Maintain Proper Composition of Cells
II. Osmoregulation
   A. Most Marine Invertebrates Are Osmoconformers
      1. Based on differential permeability of plasma membranes
      2. Osmolality is the measurement of solute concentration in a solution
         a) Moles of solute per kilogram of water
         b) Interchangeably called osmotic concentration or osmotic pressure
         c) Two solutions with same osmotic concentration are isosmotic
      3. Osmoconformer osmotic concentration of body fluid equals that of environment
      4. Are in osmotic equilibrium with environment
   B. The Problems Faced by Osmoregulators
      1. Sharks are only vertebrate osmoconformers, rest are osmoregulators   
      2. Maintain a constant osmotic concentration independent of environment
         a) Permits complex patterns of internal metabolism
         b) Requires constant adjustment
      3. Freshwater vertebrates
         a) Maintain higher salt concentration in body than in environment
         b) Hyperosmotic to the environment, water tends to enter body
         c) Must prevent water from entering and exclude excess that does enter
      4. Marine vertebrates
         a) Are hypoosmotic to the environment
         b) Body salt concentration one-third of that of the environment
         c) Must retain water to prevent dehydration
      5. Terrestrial vertebrates
         a) Bodies have a higher concentration of water than surrounding air
         b) Tend to lose water to evaporation from skin and lungs
   C. How Osmoregulation Is Achieved
      1. Simple protists and sponges
         a) Removal of water or salts coupled to removal of metabolic wastes
         b) Possess contractile vacuoles
      2. Freshwater invertebrates
         a) Utilize nephrid organs
         b) Membrane filters water and wastes; proteins and sugars retained
      3. Insects possess Malpighian tubules        
         a) Extension of digestive tract branching off hindgut
         b) Potassium ions secreted into tubules by active transport
         c) Osmotic gradient pulls body fluids and organic wastes into tubules
         d) Blood cells and proteins too large to pass across membrane
         e) Water and potassium reabsorbed through epithelium in hindgut
      4. Vertebrates utilize pressure-driven filtration system
         a) Insects secrete solutes into excretory organ to pull water through filter
         b) Higher blood pressure in vertebrate closed circulatory systems
            (1) Blood pushed through filter, proteins and large molecules retained
            (2) Water reabsorbed as filtrate passes through a long tubule
            (3) Modified filtrate excreted as urine
         c) Vertebrates selectively reabsorb small molecules
         d) Evolved various membrane channels to reabsorb different molecules
         e) Filtration and reabsorption occurs in kidney
III. The Organization Of The Vertebrate Kidney
   A. Introduction to the Renal System
      1. Functional unit is the nephron 
         a) Human kidneys are located in lower back
         b) Each contains one million nephrons            
      2. Kidney divided into outer renal cortex and inner renal medulla
      3. Series of converging tubules lead from medulla to ureter
      4. Ureter transports urine from kidney to urinary bladder
      5. Functions of vertebrate kidneys            
         a) Filtration:  blood passed through filter
         b) Reabsorption:  desirable material recaptured from filtrate
         c) Secretion:  certain ions, drugs and organic molecules transported from blood to filtrate
         d) Excretion:  materials in nephron fluid eliminated
   B. Filtration
      1. Each nephron has tubular and vascular component
         a) Vascular component is ball of capillaries called glomerulus      
         b) Embedded in first part of tubular component, Bowman's capsule
         c) Analogy of fist in soft balloon
         d) Capsule has slits through which fluid can pass


      2. Filtration process driven by hydrostatic pressure of blood against capillary walls
         a) Proteins and large molecules cannot pass through walls or capsule slits
         b) Water and small solutes are pass through
         c) Concentration of small solutes in glomerular filtrate equal to that of blood plasma
         d) Also equal to that of extracellular fluid
         e) Glomerular filtrate destined to become urine
         f) Filtered molecules will be lost if not reabsorbed
   C. Reabsorption and Secretion
      1. Most of water and dissolved solutes that enter glomerular filtrate returns to blood
         a) In human 2,000 liters of blood passes through kidneys per day
         b) 180 liters of water leaves blood, enters filtrate
         c) Most reabsorbed, only 1-2 liters becomes urine
      2. Reabsorption of water a consequence of salt reabsorption
      3. Reabsorption of glucose, amino acids, other molecules driven by active transport carriers
         a) Maximum rate of transport reached when carriers are saturated
         b) Renal glucose saturation = 180 milligrams of glucose per 100 milliliters of blood
         c) If blood glucose is higher, extra will be lost in urine
            (1) Occurs in untreated diabetes mellitus
            (2) Glucose in urine is hallmark of disease
      4. Secretion of foreign molecules and waste products
         a) Involves transport of molecules across membranes of capillaries and kidney tubules
         b) Similar to reabsorption but in opposite direction
         c) Elimination may be rapid
         d) Example:  penicillin, must be administered in high doses
   D. Excretion
      1. Potentially harmful substances eliminated via the kidney
      2. Urine also contains nitrogenous wastes
         a) Example urea and uric acid
         b) Products of amino acid and nucleic acid catabolism
      3. May also contain excess K+, H+ and other ions
         a) High H+ concentration helps maintain blood pH in narrow range
         b) Excretion of water maintains blood volume and pressure
IV. The Evolution Of Kidneys Among Vertebrates
   A. Freshwater Fishes
      1. Vertebrate kidneys evolved in bony freshwater fish             
      2. Fish body fluids have greater osmotic concentration than surrounding water
         a) Water tends to enter body from environment
         b) Solutes tend to leave body and enter environment
      3. Fish address problems by
         a) Not drinking water and excreting large volume of dilute urine
         b) Reabsorbing ions across nephron tubules from filtrate back into blood
         c) Also actively transport ions across gills from surrounding water into blood
   B. Marine Bony Fishes
      1. Bony marine fish probably evolved from freshwater ancestors
      2. Faced new problems, body fluids hypoosmotic compared to surrounding seawater
      3. Water tends to leave body by osmosis, particularly across gills
      4. Marine fish compensate by
         a) Must drink large amounts of seawater
         b) Demands on kidneys are opposite freshwater fish
         c) Must retain water and excrete ions from ingested seawater
      5. Excretion of ions
         a) Divalent calcium, magnesium, sulfate remain in digestive tract, eliminated in anus
         b) Some absorbed into blood, as are monovalent ions K+, Na+ and Cl-
         c) Most monovalent ions actively transported out of blood across gills
         d) Divalent ions secreted into nephron tubules, excreted in urine
      6. Excreted urine is isosmotic to body fluids, more concentrated than freshwater fish, less concentrated than birds and mammals
   C. Cartilaginous Fishes
      1. Virtually all except one species are marine            
      2. Solve osmotic problem differently than bony fishes
      3. Kidneys reabsorb the metabolic waste urea
         a) Have a blood urea concentration 100 times greater than mammals
         b) Thus blood is isotonic with surrounding sea              
      4. No net water movement, water loss prevented
         a) Do not drink excessive amounts of sea water
         b) Kidneys and gills do not need to remove large quantities of ions
         c) Enzymes and tissues tolerant of high urea
   D. Amphibians and Reptiles
      1. Amphibian kidneys operate identically to freshwater fish
      2. Reptile kidneys are varied with habitat
         a) Freshwater varieties have kidneys similar to fish and amphibians
         b) Marine kidneys similar to freshwater, excrete salt via salt glands on head
         c) Terrestrial forms reabsorb most of salt and water from filtrate
            (1) Conserves blood volume in dry environments
            (2) Urine cannot be more concentrated than blood plasma
   E. Mammals and Birds
      1. Produce urine with greater osmotic concentration than body fluids
         a) Can excrete wastes in smaller volume of water, water retained in body
         b) Kidneys of some dessert animals very concentrated
         c) Efficiency in kangaroo rat so efficient it never has to drink water         
      2. Loop of Henle results in production of hyperosmotic urine    
         a) Found only in birds and mammals
         b) Nephron with long loop produces concentrated urine
         c) Mammals have some long and some short looped nephrons         
         d) Birds have only short looped nephrons
            (1) Lose more body water in urine, drink more water
            (2) Marine birds drink sea water, excrete salt from salt glands near eyes        
V. How The Mammilian Kidney Retains Salt And Water
   A. Structure of Mammalian Tubule            
      1. Nephron begins in renal cortex at Bowman's capsule, receives glomerular filtrate
      2. Capsule connected to proximal convoluted tubule in renal cortex
      3. Fluid then enters loop of Henle
         a) Moves down descending limb into renal medulla
         b) Goes back up ascending limb into cortex
      4. Empties into distal convoluted tubule in cortex
      5. Drains into collecting duct that collects fluid from multiple nephrons
      6. Collecting duct plunges deep into medulla
      7. Empties contents into funnel-shaped renal pelvis
      8. Drains urine into ureter
   B. Movement of Ions and Water in the Nephron
      1. Two-thirds of NaCl and water filtered into capsule reabsorbed immediately across walls of proximal convoluted tubule
         a) Driven by active transport of Na+ out of filtrate, into blood vessels
         b) Cl- follows Na+ passively
         c) Water follows both because of osmosis
         d) Filtrate is still isosmotic to blood plasma
      2. Most of remaining third of fluid occurs in loop of Henle
         a) Serves as countercurrent multiplier
         b) Countercurrent flow exists between ascending and descending limbs of loop of Henle
      3. Six stages of countercurrent flow in region surrounding loop              
         a) Filtrate from proximal convoluted tubule passes down descending limb onto medulla
            (1) Walls impermeable to salt or urea, freely permeable to water
            (2) Surrounding extracellular fluid is hyperosmotic to filtrate
            (3) Results from high concentration of salt and urea
            (4) Water exits descending limb into surrounding tissue via osmosis
            (5) Filtrate becomes more concentrated
         b) At bottom of loop, walls become more permeable to salt, but less permeable to water
            (1) Salt diffuses out of tubule, filtrate more concentrated than extracellular fluid
            (2) Salt concentration in filtrate and extracellular fluid become equal flowing up ascending limb
         c) Higher up in thick segment of ascending arm, channels actively pump Na+ outward
            (1) Occurs against concentration gradient
            (2) Cl- passively follows, water cannot since walls are not permeable to water
            (3) Filtrate becomes more dilute toward distal convoluted tubule in cortex
            (4) Salt leaving filtrate is trapped in extracellular fluid of renal medulla
         d) Some water reabsorbed as filtrate passes through distal convoluted tubule
            (1) Filtrate now hypoosmotic to blood
            (2) Reabsorption concentrates fluid, becomes isosmotic to blood
            (3) Major solute in filtrate is urea. Most salt pumped out in ascending limb
         e) Extracellular fluid surrounding collecting duct is hyperosmotic to filtrate
            (1) Due to active extrusion of salt in ascending limb
            (2) Walls of collecting duct permeable to water
            (3) As filtrate descends into medulla through duct, water drawn out by osmosis
            (4) Filtrate becomes increasingly more concentrated through collecting duct
         f) Deep in medulla collecting duct walls become permeable to urea
            (1) Urea diffuses out of lower collecting duct into extracellular fluid
            (2) Produces high urea concentration in deep regions of medulla
            (3) Helps draw water out of descending limb of loop of Henle (stage one)
      4. Operation successful because
         a) Countercurrent flow between descending and ascending limbs
         b) Close proximity of limbs to one another
         c) Transport of salt out of ascending limb creates hyperosmotic conditions to draw water out of descending limb
         d) Loss of water increases concentration of fluid in ascending limb
            (1) Makes active transport process more effective
            (2) Helps concentrate medulla extracellular fluid
         e) Interactions create steep osmotic gradient
            (1) Gradient between renal extracellular fluid and filtrate in collecting duct
            (2) Gradient drives reabsorption of water from remaining filtrate
VI. Excretion Of Nitrogenous Wastes
   A. Animals Catabolize Nitrogen-Containing Amino Acids and Nucleic Acids
      1. Produce nitrogenous wastes that must be eliminated             
      2. Metabolism of amino and nucleic acids
         a) Amino group removed, combined with H+ to form ammonia in liver
         b) Ammonia is toxic, must be transported in very dilute solution
         c) No problem for freshwater fish with copious amounts of urine
   B. Saltwater Fish and Terrestrial Vertebrates Adapt to Transport Ammonia
      1. Must conserve body water, can't waste it to dilute ammonia
      2. Evolved three solutions
         a) Flushing
            (1) Fish breakdown protein in gills, not liver
            (2) Ammonia released there
         b) Detoxification
            (1) Mammals convert ammonia to less toxic urea in liver
            (2) Transport urea in bloodstream to kidneys for excretion
         c) Insolubilization
            (1) Birds and land reptiles convert ammonia to uric acid
            (2) Insoluble in water, crystallizes
            (3) Excreted as semi-solid paste
            (4) Mammals also excrete uric acid, but is a waste of purine nucleotide degradation
VII. The Kidney As A Regulatory Organ
   A. Regulates Osmotic Concentration of Urine Via Water Excretion
      1. Blood volume, blood pressure maintained by action of kidneys
         a) Excrete hyperosmotic urine when body needs to conserve water
         b) Excretes hypoosmotic urine when too much water has been ingested
      2. Regulate plasma Na+ and K+ concentrations
      3. Regulate blood pH
      4. Coordinated primarily via actions of two hormones:  antidiuretic hormone, aldosterone
   B. Regulation of Kidney Function by Antidiuretic Hormone
      1. Hypothalamus produces antidiuretic hormone, secreted by posterior pituitary
         a) Increase in osmolality of blood plasma stimulates its production
         b) Osmoreceptors in hypothalamus respond to elevated osmolality
         c) Trigger sensation of thirst, stimulate ADH secretion 
      2. Actions of ADH
         a) Makes kidney collecting ducts more permeable to urea
         b) Extracellular fluid in medulla is hyperosmotic to collecting duct filtrate
         c) Water leaves filtrate by osmosis, reabsorbed into blood
         d) Greater ADH secretion, ducts more permeable, more water reabsorbed
   C. Regulation of Kidney Function by Aldosterone
      1. Na+ ions are major solutes in blood
      2. If Na+ decreased, blood osmolality also decreased
         a) Inhibits ADH secretion
         b) More water excreted in urine as less is reabsorbed
         c) Blood volume decreases, lowers blood pressure
      3. Kidneys compensate for Na+ decrease via aldosterone secreted by adrenal cortex
         a) Stimulates reabsorption of Na+ at distal convoluted tubule
         b) Thus decreases amount of Na+ lost in the urine
         c) Reabsorption of Na+ followed by Cl- and then water
         d) Net effect to retain both salt and water
      4. Also promotes secretion of K+ into distal convoluted tubule
         a) Lowers blood K+ level
         b) Helps maintain K+ constant with changing amounts in diet
      5. Lack of aldosterone is lethal
         a) Excessive loss of salt and water
         b) Buildup of K+ in blood

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