Fig. 17.1
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)
Renal corpuscle = glomerulus + glomerular capsule
Renal tubule = PCT + nephron loop + DCT
Fig. 17.5
RELAVENT SPACES/COMPARTMENT SUBSTANCE MOVE THROUGH BETWEEN TUBULE AND PLASMA
Tubular fluid
(originally filtrate)
Peritubular fluid
(interstitial fluid)
Cytoplasm of
plasma
tubular cells
Renal tubule in x.s.
Peritubular capilary
in x.s.
Fig. 17.21
Renal Function is based on three process:
1. Filtration
2. Reabsorption
3. Secretion
urine
Conceptual Nephron Function/Urine formation
Filtrate – Reabsorption + secretion = Urine
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)
Reabsorption
Secretion
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
Nephron Anatomy and Processes
FILTRATION
Filtration is the basis for all
other renal events
It occurs in the renal
corpuscle
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
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
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 ↓
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
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)
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
Sympathetic Stimulation
-- This tends to over-ride influence of other factors
1. Baroreceptor reflex (for BP regulation)
–
Decreasing BP causes ↑SD and constriction of afferent arteriole
•
•
–
Increasing BP causes ↓SD and dilation of afferent arteriole
•
•
–
Decreases GFR and filtrate/urine production
Conserves fluid for blood helping maintain normal BP
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
Fig. 17.11
Table 17.1
Hormonal Regulation
• Renin—Angiotensin 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
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
• 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
• 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
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/regulated
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
Tubular reabsorption: occurs throughout the
tubule and collecting duct
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:
•
–
–
•
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
•
•
Channels
Tmax
The reabsorption of water is always passive and secondary to the movement of a solute
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.
1. Na+ actively reabsorbed
2.
Cl- passively reasbsorbed
3. H20 passively reabsorbed
Creates
concentration
gradient
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
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.
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)
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 hypokalemia—dangerous
– Ca+ reabsorption can be
influenced by parathyroid
hormone and calcitriol
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
Figure 26.15 The Effects of ADH on the DCT and Collecting Ducts
Figure 26.15
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
Regulation of Urine Volume:
regulated 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)
A Summary of Renal Function
Figure 26.16a
Figure 26.11b
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.
The Effects of ADH on the DCT and Collecting Ducts
dots represent solutes
Figure 26.15a, b
Fig. 17.20
ADH and water reabsorption
NOTE: increased plasma osmolality can also
be cause by increased solutes (Na+) in blood)
Solute
concentration
Solute
concentration
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
Table 17.3
ACID BASE REGULATION
• Homeostasis = H+ production/intake = H+ loss
• When H+ formation > H+ loss = fluids more acidic
• When H+ formation < H+ loss = fluids more alkaline
or when base increases
Normal blood pH range, acidosis, and alkalosis
Fig. 18.06
Sources of H+ in body
CO2
*
*
Volatile acid
Metabolic* and
fixed acids
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
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+
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
GENERAL BASIS FOR ACIDOSIS AND ALKALOSIS
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
Fig. 18.11
Mechanisms of Respiratory Acidosis
Failure of
receptors
Fig. 18.13
Mechanisms of Respiratory alkalosis
Fig. 18.12
Mechanisms of Metabolic Acidosis
Fig. 18.14
Mechanisms of metabolic alkalosis
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-
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
• Normal respiration is regulated by in pH of blood
Increased respirations
Decreased respirations
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
• In response to alkalosis H+ is released into blood
• 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
GENERAL COMBINED RESPONSES TO ACIDOSIS
H+ from body
fluids/plasma causing
acidosis
GENERAL COMBINED RESPONSES TO ALKALOSIS
H+ enters body
fluid/plasma