Fig. 17.1

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Fig. 17.1
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Renal Function

• Remove organic wastes (urea, creatine, uric acid)
• Control fluid volume/water balance
• Influences blood pressure
• Eliminate excess solutes from blood/control
  solute concentrations
• Regulate solute concentration
• Regulate pH

Functions performed by nephrons (within kindeys)
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Renal corpuscle glomerulus glomerular capsule
Renal tubule PCT nephron loop DCT
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Fig. 17.5
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RELAVENT SPACES/COMPARTMENT SUBSTANCE MOVE
THROUGH BETWEEN TUBULE AND PLASMA
Peritubular fluid (interstitial fluid)
Tubular fluid (originally filtrate)
Cytoplasm of tubular cells
plasma
Peritubular capilary in x.s.
Renal tubule in x.s.
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Fig. 17.21

• Renal Function is based on three process
• Filtration
• Reabsorption
• Secretion

urine
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Conceptual Nephron Function/Urine
formation Filtrate Reabsorption secretion
Urine
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Urine Production Blood Volume

• Urine is made from blood
• Increased fluid retention decreased urine
  output decreased loss of blood volume
  (stabilization of blood volume)
• Reduced fluid retention increased urine output
  increased loss of blood volume (reduced blood
  volume)

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Reabsorption
Secretion
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Processes

• Filtration
• The process in which substances from plasma leave
  blood and enter a nephron
• From blood/plasma (of glomerulus) into glomerular
  capsule ?filtrate
• Occurs in the corpuscle (glomerulus bowmans
  capsule).
• Modification of Filtrate
• Reabsorption
• Returns many substances that left glomerulus by
  filtration back into blood.
• From renal tubule into interstitial space/blood
  then into plasma of peritubular capillaries
• Occurs throughout the nephrons and collecting
  duct
• Secretion
• Eliminates additional substances from blood (of
  peritubular capillaries) by transporting them
  into renal tubule
• From blood/plasma into renal tubule
• In PCT, DCT, collecting ducts

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Nephron Anatomy and Processes
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FILTRATION

• Filtration is the basis for all other renal
  events
• It occurs in the renal corpuscle

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FILTRATION rate and composition

• We will examine two aspects of Filtration
• 1. How much filtration occurs is based on blood
  pressure
• How much filtration occures Glomerular
  Filtration Rate (GFR)
• 2. What enters filtrate (leaves blood) is based
  on size of substance

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Fig. 17.10

• The amount of filtration that occurs glomerular
  filtration rate (GFR)
• To function GFR must be
• 1. maintained within normal range despite changes
  in systemic BP
• 2. Alterable to increase or decrease water loss
  through urine

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Filtrate Formation

• Filtrate is formed when blood pressure in the
  glomerulus (glomerular hydrostatic pressure)
  causes substances to leave the glomerular
  capillaries and enter the nephron through the
  process of filtration.

• GFR is proportional to glomerular pressure
• Glomerular pressure ? ? GFR ?
• Glomerular pressure ? ? GFR ?

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Filtrate Formation

• The pressure in glomerular capillaries is
  unusually high (45-55 mmHg) because the efferent
  arteriole is narrower than the afferent arteriole.

Glomerular pressure and therefore GFR is
regulated by 1. Dilation/constriction of
afferent arteriole 2. Dilation/constriction of
efferent arteriole
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• GFR is regulated at 3 levels
• Autoregulation
• Maintains adequate GFR despite changes in blood
  flow to kidney
• due to stretching of afferent arteriole
• due to solute levels in filtrate
• ANS
• SD stimulation under periods of physical
  activity, stress, or in response to the
  baroreceptor reflex.
• Hormonal regulation
• Maintains adequate GFR despite changes in overall
  systemic BP
• Renin (Renin-Angiotensin-Aldosterone-System)

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• Autoregulation
• Smooth muscle of the arterioles responds
  automatically to glomerular pressure (Myogenic
  control)
• Increased blood pressure within afferent
  arterioles (which could lead to GFR being too
  high)
• Stretching afferent arteriole? Constriction of
  Aff Art? decreased filtration pressure ?
  decreased GFR? GFR stays within normal range
• Decreased pressure within afferent arteriole
  causes (could lead to GFR being too low)
• Less stretching of arteriole?muscle cells of Aff
  art relax? aff art dilates? increased filtration
  pressure ? increased GFR?GFR stays within normal
  range

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• Sympathetic Stimulation
• -- This tends to over-ride influence of other
  factors
• Baroreceptor reflex (for BP regulation)
• Decreasing BP causes ?SD and constriction of
  afferent arteriole
• Decreases GFR and filtrate/urine production
• Conserves fluid for blood helping maintain normal
  BP
• Increasing BP causes ?SD and dilation of
  afferent arteriole
• Increases GFR and filtrate production/urine
  output
• Eliminates excess fluid/blood volume helping
  reduce BP
• Strength of SD influence proportional to degree
  of BP change
• 2. Increases SD activity during prolonged
  exercise
• shunts blood away from kidney to other organs
  needed to support other tissues (limited
  compensation for this by autoreg)
• SD stimulation to shunt blood away from kidney
  and reduce water loss/urine output

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Fig. 17.11
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Table 17.1
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• Hormonal Regulation
• ReninAngiotensin II
• In response to decreased GFR
• Juxtaglomerular apparatus (macula densa) releases
  renin
• Renin?angiotensin II
• Angiotensin II? vasoconstriction of efferent
  arteriole
• Increases glomerular pressure and GFR
• (also produces widespread systemic
  vasoconstriction to increase systemic BP)
• Atrial Natriuretic Peptide (ANP)
• Increased BP? stretch of atria walls
• Atria release ANP
• ANP ? dilation of afferent arteriole
• Dilation of afferent arteriole? Increased GFR?
  increasing urine production/water loss?
  decreasing Blood volume? BP goes down

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FILTRATION What gets filtered (composition of
filtrate)

• What enters filtrate (leaves blood) is based
  mostly on size of substance
• If substance is small enough to fit through gaps
  in glomerular capillaries and gaps between
  podocytes it will leave plasma, enter the
  corpuscle, and become filtrate

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• Plasma proteins (e.g., albumin), formed elements,
  and other proteins are too big to cross out of
  glomerulus
• Water, ions, amino acids, glucose, urea, uric
  acid, creatine and other small organic molecules
  are small enough to leave glomerulus and become
  filtrate

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• When created the filtrate is isosmotic with
  interstitial fluid/peritubular fluid
• The solute concentration of filtrate and plasma
  is the same
• See below and next slide

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Filtrate Modification

• Reabsorption
• Substances move from filtrate into interstitial
  space/blood.
• Occurs throughout the nephrons and collecting
  duct
• Primary location of reabsorption is the proximal
  tubule
• Re-captures substances that entered filtrate by
  that the body needs to retain/keep.
• Based largely on passive diffusion and presence
  of various transport proteins
• Transport proteins may be limited in reabsorptive
  capacity
• Reabsorption can be selective in different
  regions based on which transport proteins are
  present
• Reabsorption can be hormonally influenced/regulate
  d

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Filtrate Modification

• Secretion
• Moves substances from blood into filtrate
• Eliminates/removes from blood substances that did
  not enter the filtrate or need to be eliminated
  at greater levels then achieved by filtration
  alone.
• Typically based on transport proteins
• Can be hormonally modified/regulated

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Tubular reabsorption occurs throughout the
tubule and collecting duct
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The PROXIMAL CONVOLUTED TUBULE primary site of
reabsorption

• Filtrate entering the PCT has a composition
  similar to plasma
• The PCT Will
• Reabsorbs 60-70 of filtrate (108L of filtrate)
• Reabsorbs 99 of organic nutrients
• E.g., Glucose, amino acids
• Reabsorption occurs through a complex combination
  of
• Active transport of ions creating gradients that
  power
• Passive movement through
• Channels
• Facilitate transport
• Cotransport
• Because the solute transport occurs through
  transport proteins each of which is specific to
  only one or several solutes
• The reabsorption of specific solutes can be
  selectively regulated
• The transport proteins can potentially be
  saturated creating a maximum limit of how much of
  a solute can be reabsorbed
• Tmax
• The reabsorption of water is always passive and
  secondary to the movement of a solute

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• One set of reabsorption relationships is as
  follows
• Na is reabsorbed with pumps/active transport
  creating a electrical gradient
• Cl- (an other anions) follows passively
  (attracted by charges)
• Water then follows solutes.

• Na actively reabsorbed
• 2. Cl- passively reasbsorbed
• 3. H20 passively reabsorbed

Creates concentration gradient
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• Other routes of transport in PCT
• Glucose and amino acid reabsorption by
  co-transport with sodium
• H secretion via counter transport
• HCO3- reabsorbed with Na cotransport
• Na reabsorption w/ K countertransport
• Secretion of various substances also occurs at
  the PCT but those will be considered later on a
  case-by-case basis

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• Nephron loop (loop of henle)
• The descending limb is permeable to water, but
  not to solutes
• The ascending limb is relatively impermeable to
  water, but reabsorbs/pumps out Na and K
• The Na and K pumped out of descending limb
  creates a high solute concentration in
  surrounding interstitial fluid/peritubular fluid
  that causes water to passively be reabsorbed from
  the descending limb.
• This all results in a tubular fluid that is more
  concentrated with solutes by the time it reaches
  the end of the ascending limb.

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Distal Convoluted Tubule

• Receives only 15-20 of original fluid of
  filtration
• Variable reabsorption under the direction of
  hormones
• Variable secretion of ions and xenobiotics
  (foreign molecules)

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Distal Convoluted Tubule Reabsorption

• Reabsorption in the DCT is mostly Na and Ca
  under hormonal control
• Aldosterone causes increased production of
  incorporation of Na reabsorption proteins
• Because Na is counter-transported for K,
  prolonged high aldosterone levels can lead to
  hypokalemiadangerous
• Ca reabsorption can be influenced by parathyroid
  hormone and calcitriol

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DCT Secretion

• When the concentration of some substances becomes
  high in blood, they diffuse into peritubular
  fluid where they will be picked up by tubular
  cells and transported into the renal tubule
• Key substances Secreted include
• K
• High blood K causes K secretion in exchange for
  Na (it is gradient driven)
• By Na/K co-exchange
• H
• When blood becomes acidic peritubular cells
  secrete H into tubular fluid
• The resulting HCO3- is transported into the
  peritubular fluid and then enters blood where it
  buffers pH
• One H secretion pathway is Na
  reabsorption/aldosterone linked
• So prolonged increased aldosterone can cause
  alkalosis

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Figure 26.15 The Effects of ADH on the DCT and
Collecting Ducts
Figure 26.15
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Collecting Duct DCT

• Variable amounts of secretion
• Variable amounts of reabsorption
• We will focus on role of CD in water reabsorption
  and control of urine volume

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Regulation of Urine Volumeregulated through Na
reabsorption and water permeability

• Urine originates with the filtrate
• If it is in urine, then it originally came from
  blood
• Normal urine output 1.2L/day
• Increase urine output
• Increased water to solute ratio
• Increased water loss from body (potential blood
  volume decrease)
• Decreased urine output
• Decreased water to solute ration
• Decreased water loss from body (stabilizes blood
  volume)

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A Summary of Renal Function
Figure 26.16a
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Figure 26.11b
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Urine Volume is Regulated primarily by ADH (in
conjunction with aldosterone)

• ADH causes increased water permeability of DCT
  and CD
• Causes incorporation of aquaporins
• Increased ADH Results in
• increased water reabsorption
• Concentrates urine
• Less water lost from plasma
• Aldosterone enhances this by increasing the
  solute concentration of the peritubular fluid
  through increased Na reabsorption.

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The Effects of ADH on the DCT and Collecting
Ductsdots represent solutes
Figure 26.15a, b
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Fig. 17.20
ADH and water reabsorptionNOTE increased
plasma osmolality can also be cause by increased
solutes (Na) in blood)
Solute concentration
Solute concentration
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ADH (vasopressin)

• ADH released by Post Pit when osmoreceptors in
  hypothalamus detect high osmolality
• From excess salt intake or dehydration
• Causes thirst
• Stimulates H2O reabsorption from urine
• Homeostasis maintained by these countermeasures

14-25
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Table 17.3
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• ACID BASE REGULATION
• Homeostasis H production/intake H loss
• When H formation gt H loss fluids more acidic
• When H formation lt H loss fluids more
  alkaline

or when base increases
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Normal blood pH range, acidosis, and alkalosis
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Fig. 18.06

• Sources of H in body

CO2


Volatile acid
Metabolic and fixed acids
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Buffers temporarily minimize pH changes
(neutralize H) This minimizes pH changes and
damages to local tissues They do NOT eliminate
H Lungs and Kidneys REMOVE H from body
Also present in ICF but most important in ECF
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Bi-carbonate Buffer System

• From organic and fixed acids
• NOT from CO2 production of aerobic respiration
• in this process H are fixed as part of H20
  and bicarbonate is reformed with the
  elimination of CO2 from body

Eliminated through ventilation/exhalation
regenerates HCO3- which accepts/buffer more H
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• Acid base balance can maintained by
• First existing buffer systems
• These work instantaneously
• Limited (when all buffers are bound this system
  stops working)
• Second physiological activity of
• 1) respiratory system (responds in minutes,
  begins compensating within minutes)
• 2) renal systems (responds in hours to days)which
  can compensate through
• Secretion or absorption H
• Secretion or absorption of acids and bases
• Generation of additional buffers

Accomplished by respiratory and renal
compensations
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GENERAL BASIS FOR ACIDOSIS AND ALKALOSIS
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• Types of pH imbalances
• Respiratory acidosis resp system failure to
  eliminate sufficient CO2 (? hypercapnia ? low pH)
• Most common
• Respiratory alkalosis
• Too much CO2 eliminated (through
  hyperventilation)
• ? hypocapnia ? high pH
• Generally uncommon, but happens routinely at high
  altitude
• Metabolic Acidosis
• Commonly due to increase lactic acid and ketone
  bodies
• Inability to secrete H at kidneys severe
  bicarbonate loss
• Second most common
• Metabolic alkalosis
• Relatively uncommon
• Elevated levels of HCO3
• Combined metabolic and respiratory acidosis
• Caused because oxygen started tissues perform
  anaerobic respiration

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Fig. 18.11
Mechanisms of Respiratory Acidosis
Failure of receptors
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Fig. 18.13
Mechanisms of Respiratory alkalosis
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Fig. 18.12
Mechanisms of Metabolic Acidosis
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Fig. 18.14
Mechanisms of metabolic alkalosis
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• Renal and Respiratory Compensation
• responses to acidosis or alkalosis
• Respiratory System
• Alter breathing rate to
• Remove H by tying them up in H2O
• Producing HCO3-
• Renal/Urinary System
• Secrete H into urine
• Reabsorb HCO3-

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• Limitations of bicarbonate buffer system
• Cannot protect against pH changes due to CO2
• Works only when respiratory system is working
• Limited by availability of bicarbonate
• Sources of bicarbonate are the NaCO3 reserve
• Bicarbonate reabsorption by kidney

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• Respiratory Influences/Compensations
• Breathing/ventilating
• Eliminates H and maintains available HCO3
• Increased breathing rate/ventilation ? more
  bicarbonate and less H ? decreased acidity
  (i.e., more alkaline)
• Decreased breathing rate/ventilation ? less
  bicarbonate and more H ? increased acidity
• Takes minutes to compensate for significant
  changes in plasma pH

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• Normal respiration is regulated by in pH of blood

Increased respirations
Decreased respirations
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• Renal Influences/Compensation
• Kidneys normally
• Secrete H or add H to blood
• Ability to do so is limited by buffers in
  filtrate which help maintain H gradient
• Reabsorb HCO3 (enters blood as NaHCO3)
• These activities are dependent on carbonic
  anhydrase
• Take days (1-3 d) compensate for significant
  changes in plasma pH

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• In response to alkalosis H is released into
  blood

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• Secretion of H into tubular fluid paired with
  release of HCO3- into blood
• In starvation state, glutamine is metabolized
  causing release of HCO3- into blood

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• GENERAL COMBINED RESPONSES TO ACIDOSIS

H from body fluids/plasma causing acidosis
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• GENERAL COMBINED RESPONSES TO ALKALOSIS

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