RenalDigestive Physiology Unit 1 - PowerPoint PPT Presentation

Title: RenalDigestive Physiology Unit 1


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Renal/Digestive PhysiologyUnit 1

• Dr. Jill M. Davis

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Urinary System Anatomy

• Kidney external anatomy
• Lie retroperitoneally on the posterior abdominal
  wall
• They lie between the T12 L3 vertebrae the
  right kidney is typically 1-2 cm inferior to the
  left one.
• The hilum on the medial concave surface of the
  kidneys serve as and entrance/exit point for
• Renal artery
• Renal vein
• Ureter
• Renal nerve plexus (mainly SNS)

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Urinary System Anatomy

• Kidney Internal Anatomy
• Renal pelvis
• Major and minor calyces
• Renal medulla
• Renal pyramids
• Papilla
• Renal cortex

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Kidney Microanatomy

• Nephron
• There are approximately 1 million nephrons/per
  kidney
• Bowmans capsule
• Proximal convoluted tubule
• Loop of Henle
• Short in cortical nephrons, long in
  juxtamedullary nephrons
• Distal convoluted tubule
• Collecting tubule/duct

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Renal Blood Supply

• Renal artery ? segmental arteries ? interlobar
  arteries ? arcuate arteries ?interlobular
  arteries ? afferent arteriole ? glomerulus ?
  efferent arteriole ? peritubular capillaries /
  vasa recta ? interlobular veins? arcuate veins ?
  interlobar veins ? segmental veins ? renal vein

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Kidney Functions

• Acid base balance
• Electrolyte balance
• Elimination of metabolic waste
• Elimination of hormones and drugs
• Role in gluconeogenesis
• Endocrine function (EPO, renin)
• Vitamin D activation
• Blood pressure regulation / water balance

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Nephron function

• Excretion filtration secretion - reabsorption

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Chapter 25 Body Fluid Compartments

• Total body water
• The sum of all fluid found in the body (42 liters
  or 60 of body weight)
• Variations due to body size, gender, age, obesity
• Extracellular fluid compartment
• Plasma (3 L) not including blood cells
• Interstitial Fluid (11 L)
• Intracellular Fluid (28 L)
• Transcellular Fluid
• Includes synovial, peritoneal, pericardial, CSF,
  intraocular fluid (1 L)

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Barriers Between Fluid CompartmentsFig 25-1

• Capillary Membrane
• Barrier between the plasma and interstitial fluid
  compartments.
• Cell Membrane
• Barrier between the interstitial fluid
  compartment and intracellular fluid.

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Water Intake and Output

• To maintain homeostasis, water intake must
  balance water output
• Sources of Water
• Ingestion (about 2100 ml/day)
• Absorbed from the GI tract (mainly the large
  intestine) into the plasma compartment
• Synthesis
• Oxidation of carbohydrates (200 ml/day)
• Contributes to intracellular fluid

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Water intake and output

• Water loss
• Insensible water loss
• Evaporation through ventilation and through the
  skin (700 ml/day)
• Does NOT include sweat
• Sensible water loss
• Sweat depends on ambient temperature and
  physical activity (normally 100 ml/day can
  increase to 1-2 L per hour with heavy sweating)
• Feces 100 ml/day, increases with diarrhea
• Kidneys (excretion of urine) 1400 ml/day

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Composition of Plasma and Interstitial Fluid

• Plasma and interstitial fluid is similar
• Capillary wall is highly permeable to water and
  ions, but not very permeable to proteins
• The protein concentration of plasma is higher
  than interstitial fluid (albumin, lipoproteins,
  antibodies etc.)
• Donnan effect because plasma proteins have a
  net negative charge, there are slightly more
  cations in the plasma than in the interstitial
  fluid.

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Composition of Intracellular Fluidfig 25-2

• The plasma (cell) membrane is not permeable most
  ions and protein, therefore there are many
  differences between ECF and ICF.
• ECF higher in Na, Cl-, HCO3-
• ICF higher in K, PO4-3, Mg2, organic anions,
  protein

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Measurement of Body Fluid Compartments

• Direct measurements
• Total body water 3H20 or 2H20
• Extracellular fluid radioactive Na or inulin
• Plasma Volume I125 albumin, Evans blue dye
• Indirect measurements
• Intracellular fluid TBW-ECF volume
• Interstitial fluid volume ECF volume plasma
  volume
• Blood volume plasma vol / 1-HCT

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Definitions

• Osmosis diffusion of water across a selectively
  permeable membrane from a region of high H20 to
  a region of low H20
• Moles vs. Osmoles
• mole 6.022 x 1023 particles of solute
• Osmole a mole of osmotically active particles
  of solute
• Example one mole of NaCl 2 osmoles of
  osmotically active particles.
• Osmolality vs osmolarity
• Osmolality moles / kg water
• Osmolarity moles / L of water

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Definitions

• Osmotic pressure amount of pressure needed to
  oppose osmosis
• Osmotic pressure (p) is related to osmolarity
• p CRT (vant Hoffs law)
• C concentration of solutes (Osm/L)
• R ideal gas constant
• T temperature (K)
• 1 mOsm/L gradient across a membrane exerts an
  osmotic pressure of 19.3 mm Hg.

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Isotonic/Hypotonic/Hypertonic Solutions(Isosmotic
/hypo-osmotic/hyperosmotic)

• The osmolarity of ICF is approximately 282 mOsm/L
• Therefore, if a cell is placed in pure water
  there would be an osmotic pressure of 5400 mm Hg.

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Predict the effect of injecting isotonic,
hypertonic, and hypotonic solutions into the ECF
space
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Plasma Osmolarity

• Plasma sodium concentration is a good indicator
  of plasma osmolarity.
• Hyponatremia
• Hypo-osmotic dehydration (Na loss)
• Diarrhea or vomiting
• Diuretic overuse
• Decreased aldosterone (Addisons disease)
• Hypo-osmotic overhydration (H2O gain)
• Increased ADH secretion

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Continued.

• Hypernatremia
• Hyperosmotic dehydration (H2O loss)
• Decreased ADH (diabetes insipidis)
• Increased sweating (gt water intake)
• Hyperosmotic overhydration (Na gain)
• Increased aldosterone

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Edema Terminology

• Non-pitting lymphedema
• Congenital defect in lymph system development
• Acquired
• trauma to lymph system (i.e. surgery)
• Infection
• Myxedema hypothyroidism
• Pitting most common form
• Grading system
• 1 2mm 2 4mm 3 6mm 4 8mm

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Edema Terminology

• Intracellular edema
• Ischemia ? decreased nutrition ? decreased
  metabolism ? decreased ion pump function ?
  increased intracellular Na ? increased H2O ?
  intracellular edema
• Extracellular edema
• Increased capillary permeability (inflammation)
• Lymphatic blockage

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Edema Terminology

• Peripheral edema edema in somatic structures
  (non-visceral)
• Dependant edema swelling accumulates in lower
  areas due to effects of gravity
• Effusion fluid accumulation in potential
  spaces
• Ascites peritoneal cavity
• Pleural effusion pleural cavity
• Anasarca severe generalized edema

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Prevention of Edema

• Low compliance of interstitium in negative
  pressure range
• Ability to increase lymph flow
• Washdown effect

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Glomerular Capillary Structure

• Three layers
• Endothelium with fenestrae
• Basement membrane, negative charge
• Podocyte epithelium with slit pores, negative
  charge
• Glomerular capillaries prevent filtration of
  protein and blood cells under high filtration
  pressures.
• Filterablility is based on size and charge of the
  solute.

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Glomerular Filtration Rate

• GFR Kf X Net filtration pressure
• GFR glomerular filtration rate
• Kf glomerular capillary filtration coefficient
  (product of surface area and permeability)
• Net filtration pressure sum of Starlings
  forces.

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Glomerular Filtration Rate

• GFR Kf x (PG PB pG pB)
• PG Glomerular hydrostatic pressure
• PB Bowmans capsule hydrostatic pressure
• pG Glomerular colloid osmotic pressure
• pB Bowmans capsule colloid osmotic pressure
  (normally 0)

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Regulation of GFR

• Kf not used for regulation, but diseases can
  effect Kf
• Diabetes
• Chronic hypertension
• Kidney diseases generally decrease Kf
• PB also not used for regulation, but diseases
  can effect PB
• Urinary tract obstruction

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Regulation of GFR

• pB in a healthy state equals zero, however
  disease can alter pB
• Proteinurea / albuminurea

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Regulation of GFR

• pG changes during filtration
• Plasma protein concentration increases as blood
  passes from the afferent to efferent arteriole

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Regulation of GFR

• Filtration fraction GFR/renal plasma flow
• ? flow ? filt fract therefore ? pG ?GFR
• ? flow ? filt fract therefore ? pG ? GFR
• Even with no change in hydrostatic pressure,
  changing renal plasma flow effects GFR

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Regulation of GFR

• The primary means by which GFR is regulated is by
  changing PG.
• ? PG increases GFR
• ? PG decreases GFR
• Glomerular hydrostatic pressure is determined by
• Arterial pressure
• Afferent arteriolar resistance
• Efferent arteriolar resistance

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Regulation of GFR

• ? arterial pressure - ?GFR
• Keep in mind that autoregulation keeps a fairly
  even glomerular pressure
• ? Afferent arteriole resistance (constriction) ?
  GFR
• Moderate ? Efferent arteriole resistance
  (constriction) ?GFR
• Large ? Efferent arteriole resistance
  (constriction) ?GFR (biphasic response)

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Regulation of GFR

• Sympathetic effect on GFR
• Causes vasocontriction of renal arterioles and
  decreases renal blood flow, thereby decreasing
  GFR
• Effects are very minimal at normal levels of
  sympathetic tone, but during acute severe
  increases in sympathetic activity, GFR can
  decrease significantly.

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Regulation of GFR

• Hormones
• Norepinephrine and epinephrine (from adrenal
  medulla) constrict renal arterioles causing
  decreased GFR and renal blood flow. As with the
  SNS, only in acute severe conditions is there
  much affect.
• Endothelin is a vasoactive peptide released
  when there is damaged vessels, and causes
  vasoconstriction. It may contribute to kidney
  failure in disease states where endothelin is
  secreted.

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Regulation of GFR

• Angiotensin II constricts efferent arterioles
• Is a circulating hormone
• Also is secreted locally by the kidneys
  (autocoid)
• Angiotensin II is generally produced when there
  is reduced blood pressure, or decreased blood
  volume.
• Constricting efferent arterioles increases
  glomerular pressure, maintaining kidney function.
• It also slows blood flow in the peritubular
  capillaries which increases reabsorption of Na
  and water.

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Regulation of GFR

• Endothelial derived relaxing factor (NO)
• Autocoid that decreases renal vascular
  resistance.
• It is secreted tonically to help maintain normal
  level of vasodilation.

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Autoregulation of Renal Blood flow and GFR

• Purpose of regulating renal blood flow is to
  maintain a relatively normal GFR, even when
  systemic blood pressure changes.
• Normal GFR occurs in MAP ranges from 75 160 mm
  Hg. (fig 26-16)

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Autoregulation of Renal Blood flow and GFR
consider the following

• Normal
• MAP 100 mm Hg
• GFR 180 L/day
• Reabsorption 178.5 L/day
• Excretion 1.5 L/day

• Small change in blood pressure
• MAP 125 mm Hg
• GFR225 L/day
• Reabsorption 178.5 L/day
• Excretion 46.5 L/day

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Tubuloglomerular Feedback

• Juxtaglomerular complex (apparatus) This
  feedback mechanism uses special cells in the
  distal tubule and the afferent and efferent
  arterioles
• Distal tubule macula densa senses NaCl
  concentration
• Afferent and efferent arterioles
  juxtaglomerular cells
• (figure 26-17)

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Chapter 27 Tubular Processing

• Principles of tubular reabsorption (fig 27-1)
• Two pathways through tubular epithelium
• Transcellular (carrier mediated)
• Pericellular (tight junctions)
• Transport mechanisms
• Active transport
• Secondary active transport
• Passive transport
• Osmosis
• Bulk flow

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Tubular Tubular Processing

• Primary active transport
• Sodium potassium ATPase
• Located on the basolateral membranes of tubular
  epithelial cells
• Creates a Na gradient (low intracellular sodium)
• Creates a negative membrane potential
• Passive transport of sodium
• Therefore, Na diffuses passively either
  transcellularly, or pericellularly due to the
  above gradients.
• See fig 27-2

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Tubular Processing

• Other primary active transport carriers
• Hydrogen ATPase
• Hydrogen-potassium ATPase
• Calcium ATPase

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Tubular Processing

• Secondary active transport
• Na gradient caused by the Na/K ATPase drives
  coupled transport (Na with another solute)
• Na/Glucose carrier
• Na/amino acid carriers
• See fig 27-3 (top)

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Tubular Processing

• Secondary active secretion
• Is the secondary active transport of a substance
  in the opposite direction (antiport)
• H can be secreted using this mechanism
• See fig 27-3 (bottom)

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Tubular Processing

• Osmosis
• The only mechanism that causes reabsorption of
  water is osmosis
• Osmotic gradient is created principally by the
  primary and secondary active reabsorption of
  solutes such as Na.
• Water moves by osmosis either transcellularly or
  pericellularly (assuming that part of the nephron
  is permeable to water)
• Solvent drag rapid H2O reabsorption brings
  other solutes with it.

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Tubular Processing

• Bulk flow
• Also known as ultrafiltration
• Governed by hydrostatic and colloid osmotic
  pressures.

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Tubular Processing

• Other passive reabsorption
• Due to the active reabsorption of Na, and the
  subsequent osmosis of water, other solutes become
  concentrated in the tubule lumen
• Therefore, these solutes are reabsorbed.
• Examples urea and Cl-
• See fig 27-5

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Tubular ProcessingSummary of processing of
selected substances

• Substance Filt reab ex
• Glucose 180 g/day 180 0
• Bicarbonate 4320 mEq/day 4318 2
• Sodium 25560 mEq/day 25410 150
• Chloride 19440 mEq/day 19260 180
• Potassium 756 mEq/day 664 92
• Urea 46.8 g/day 23.4 23.4
• Creatinine 1.8 g/day 0 1.8

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Tubular Processing

• Transport maximum
• For some substances, there is a maximum rate by
  which they can be reabsorbed
• Due to saturation of transport carriers with
  excessive tubular (filtered) loads
• Result is abnormally increased excretion of that
  substance
• Example glucose reabsorption in uncontrolled
  diabetes mellitus
• See fig 27-4

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Proximal Convoluted Tubule

• Histology
• Cells have a lot of mitochondria
• Brush border on apical (luminal) side
• Basal channels (on basolateral side)

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Early Proximal Tubule

• Na/K pump
• 2 cotransport
• Na / glucose symport (100 reabsorption)
• Na / amino acids symport (100 reabsorption)
• Na / H antiport (H secretion)
• HCO3- absorption (mechanism chapter 30)
• Aquaporin I water reabsorption via osmosis

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Late Proximal Tubule

• Continued Na/K pump
• Passive transport Cl-
• Active secretion of organic acids and bases (i.e.
  bile salts, oxalate, urate, catacholamines)
• Active secretion of drugs and toxins

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Proximal Tubule

• By the time the filtrate reaches the end of the
  Proximal tubule, 65 of H20, Na, Cl, K are
  reabsorbed, and all the glucose and a.a.
• The proximal tubule is isosmotic

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Loop of Henle

• Histology
• Thin descending limb
• Thin ascending limb
• Thick ascending limb

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Loop of Henle

• Thin descending limb
• Very permeable to H20
• Somewhat permeable to solutes
• No active reabsorption
• Thin ascending limb
• Impermeable to H20

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Loop of Henle

• Thick ascending limb
• Also impermeable to H20
• Na/K pump
• Na/H antiport (H secretion)
• 1-Na, 2-Cl-, 1-K co-transporter (reabsorption
  of these three ions)(target for loop diuretics)
• Paracellular reabsorption of Mg, Ca, Na, and
  K (due to electrochemical gradient)
• The thick limb is hypo-osmotic

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Distal Convoluted Tubule

• Early Distal tubule
• Characteristic similar to thick ascending loop of
  Henle
• Contains a Na/Cl cotransporter that is sensitive
  to thiazide diuretics

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Distal Convoluted Tubule

• Late distal tubule (and cortical part of
  collecting duct)
• Principal Cells
• Na/K pump
• Sodium resorption (passive) sensitive to
  aldosterone
• Potassium secretion (passive) sensitive to
  aldosterone
• Sensitive to K sparing diuretics
• With ADH is permeable to water (reabsorption)

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Distal Convoluted Tubule

• Late distal tubule (and cortical part of
  collecting duct) continued
• Intercalated cells
• Reabsorbs K
• secretes H (H ATPase)
• Secretes HCO3-

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Medullary Collecting duct

• Small amount of H20 and Na reabsorption
• Passive reabsorption of Cl-
• Also sensitive to ADH
• Is permeable to urea (some reabsorption)
• Also has an H ATPase (secretion)

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Glomerulotubular Balance

• This refers to the balance between GFR and
  reabsorption as GFR goes up, so does
  reabsorption.
• This is the second line of defense against large
  changes in GFR
• Recall the first line of defense was
  glomerulotubular feedback aka renal
  autoregulation.
• Governed by hydrostatic and colloid osmotic
  forces of the IF and peritubular capillaries.

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Peritubular Capillary Reabsorption

• Reab. Kf x net reabsorption force
• Net reabsorption influenced by same Starlings
  forces
• Pc
• Pif
• pc
• pif
• Net movement is into peritubular capillaries
  (fig. 27-15)

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Peritubular Capillary Reabsorption

• Effects on Pc (peritubular)
• ? MAP ? ?Pc ? ?reabsorption
• ?afferent art. resistance ?Pc ? ? reab
• ?efferent art. resistance ?Pc ? ? reab
• Effects on pc (peritubular)
• ? plasma protein ? ? pc ? ?reabsorption
• ? filtration fraction ? ? pc ? ? reabsorption
• Effects on Kf
• Generally doesnt change, but
• ? in Kf ? ? reabsorption

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Peritubular Capillary Reabsorption

• Pif and pif changes with Pc and pc
• As Pc increases, Pif increases
• As pc decreases, pif decreases
• Interstitial fluid pressures in turn affect
  reabsorption through the tubular epithelium.
• See fig. 27-16. (note backleak)
• Therefore, peritubular capillary reabsorption
  equals tubular reabsorption

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Hormones and control of Reabsorption

• Aldosterone
• Secreted by zona glomerulosa cells of the adrenal
  cortex
• Promotes Na reabsorption and K secretion
• Target principle cells of the cortical collecting
  tubules
• Mechanism
• Stimulates Na/K pump on basolateral membrane
• Increases Na permeability of luminal membrane

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Hormones and Control of Reabsorption

• Angiotensin II
• Secreted by liver as angiotensinogen converted
  by renin into angiotensin I, then to Angiotensin
  II by ACE in the lungs.
• Effects
• Increases aldosterone secretion
• Constricts efferent arterioles decreasing Pc of
  peritubular capillaries and increases
  reabsorption
• Stim Na/K pump, and Na/H exchanger, therefore a
  lot of Na is reabsorbed.

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Hormones and Control of Reabsorption

• ADH
• Secreted by posterior pituitary gland
• Increases water permeability of distal tubules
• Mechanism causes insertion of aquaporin-2 into
  tubular membrane.
• Atrial Natriuretic Peptide
• Secreted by distended atria
• Decreases Na and water reabsorption
• PTH
• Increases reabsorption of Ca in the distal tubules

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Measurement of Renal Clearance

• Definition of Clearance
• The volume of plasma that is completely cleared
  of a substance by the kidneys per minute
• This is a theoretical value, as it is impossible
  to completely clear a substance from a given
  volume of plasma.

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Measurement of Renal Clearance

• Consider the following
• let Cs clearance rate of substance
  (ml/min) and
• Let Ps plasma s (mg/ml)
• Therefore Cs x Ps the amount of substance that
  moves from the plasma into the tubules (mg/min)

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Measurement of Renal Clearance

• Also consider
• Let V urine flow rate (ml/min) and
• Let Us urine s (mg/ml)
• Therefore Us X V rate of movement of substance
  from the tube into the urine, or the excretion
  rate (mg/min)

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Measurement of Renal Clearance

• IF a substance is freely filtered, but not
  reabsorbed or secreted, then
• Cs x Ps Us x V
• Which is saying that the mg/min of clearance of a
  substance from the plasma into the tubules is the
  same as the mg/min of the substance showing up in
  the urine (excretion).
• Rearranging the equation, we can measure the
  renal clearance (Cs)Cs Us x V / Ps

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Measurement of Renal Clearance

• Since Cs is essentially the same as GFR, the
  equation can be re-written as
• GFR Us x V / Ps
• Inulin can be used to measure GFR
• See figure 27-17

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Measurement of Renal Clearance

• Creatinine can also be used
• It is produced by the body, so it doesnt need to
  be injected
• drawback it is secreted in small amounts in the
  kidney tubules
• correction measurement of Pcreatinine
  overestimates its concentration by about the
  amount it is secreted, so creatinine is still a
  good indicator of GFR.

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Measurement of Renal Clearance

• One can compare inulin clearance with other
  substances.
• If the clearance of a substance is equal to
  inulin, then the substance is filtered, but not
  reabsorbed or secreted
• If the clearance of a substance is less than
  inulin, then the substance is reabsorbed
• If the clearance of a substance is greater than
  inulin, then the substance is secreted.
• Often expressed as a clearance ratio Cs / Cinulin