Functions of the kidneys
1)
Regulates ionic compositions of blood
2)
Regulates blood pH
3)
Regulates blood volume
4)
Regulates blood pressure
5)
Maintains blood osmolarity
6)
Produces hormones
7)
Regulates blood glucose levels
8)
Excretes wastes and foreign substances
Why is it important for the kidneys to regulate blood pH?
Because proteins fold at specific pH
How do kidneys relate to blood volume?
- works with the heart
- Higher BV, kidneys excrete more water
- Lower BV, kidneys excrete less water
How do kidneys relate to blood pressure?
- The kidneys respond to baroreceptors and volume receptors
- works with the heart
How do kidneys relate to maintaining blood osmolarity?
- closely linked to regulating ionic compositions of blood
- normal osmolarity ~300 mOsm (all solutes dissolved in blood, not just ions)
What hormones do the kidneys produce?
- produces erythropoietin
- converts Vitamin D into
calcitrol
(active form)
How do kidneys help to regulate blood glucose levels?
the kidneys can carry out gluconeogenesis
What are some of the substances that the kidneys excrete?
- urea
- uric acid
- creatinine
- urobilin (from break down of hemoglobin)
Where are there kidneys located?
The 2 kidneys are located on either side of the spine, posterior to the abdomen, ~11th/12th rib. Therefore, the kidneys are located in the
retroperitoneal cavity
.
What is the renal pelvis?
where urine is collected
What are the calyces?
Pyramid-like structures at the bottom of the medulla that funnels the processed urine into the renal pelvis
How much of the cardiac output d the kidneys receive (each)?
20% of the cardiac output each
Define nephron
the functional unit of the kidney
How many nephrons do each kidney have?
~1 million nephrons each
Name the 2 basic structures of the nephron
- Renal corpuscle
- tubule
Main responsibility of renal corpuscle
filter blood
General responsibility of the tubule
processes the filtered fluid
Difference between filtrate and urine?
filtrate is in the nephron and urine in the after collecting duct
Name the 2 types of nephrons in the kidneys
- Cortical Nephron
- Juxtamedullary Nephron
Describe Cortical Nephrons
- 80% of nephrons in humans
- shorter loop of Henle, mostly in the cortex
- as a
peritubular capillary bed
Describe Juxtamedullary nephron
- long loop of Henle, mostly in medulla
- Vasa recta capillary bed
Describe the vasa recta capillary bed of the juxtamedullary nephron
- parallel with the loop of Henle
- helps maintain the increasing osmolarity of the medulla of the kidney
Where are the renal corpuscles located?
The renal corpuscles of all nephrons are located in the cortex of the kidney
Name the two main structures of the renal corpuscle
- Bowman's capsule
- glomerulus
Describe the Bowman's capsule
- fluid filled hollow ball-like structure
- surrounds glomerulus
- made of epithelial cells that is continuous with the proximal tubule
Describe the glomerulus
- specialized structure of "leaky" capillaries due to having many fenestrae (pores)
- endothelium is fused with the epithelium of Bowman's capsule
Describe the purpose of the basal lamina in the glomerulus
- basal lamina is the layer of ECM connecting the endothelium and the epithelium of Bowman's capsule
- serves as a rough sieve for filtering
- excludes nearly all plasma proteins
What are podocytes?
They are specialized epithelial cells that acts as a third filtering component of the renal corpuscle.
Describe the appearance of podocytes.
- they have long foot-like processes that interlace with one another around the glomerulus capillaries
- leaves narrow sllits that help to control the rate of fluid filtration into Bowman' capsule
- damage can lead to an increase filtration of fluid
What is urinalysis?
Uses urine test strips that use colorimetric reactions to indicate the presence or absence of substances in the urine.
What should not be filtered into the urine?
- leukocytes
- nitrites
- protein
- haemoglobin
- ketones
- bilirubin
- glucose
What is normal urine pH?
6
What is specific gravity?
It looks at the concentration of urine
What does high specific gravity indicate?
A higher specific gravity indicates more concentrated urine
and that the individual is dehydrated.
Describe the epithelial cell type in proximal tubule
consists ONLY of
simple columnar epithelium
with microvilli and many mitochondria
Describe the epithelial cell type(s) in the descending limb of the loop of Henle
consists ONLY of
simple squamous epithelium
with some microvilli but they are not as metabolically active
Describe the epithelial cell type(s) in the collecting duct
It has a mixed population of cuboidal cells:
-
principal cells
-
Intercalated cells
Describe the principal cells of the collecting duct
- highest #
- reabsorbs
- responsive to hormone
- metabolically active
Describe the intercalated cells of the collecting duct
- balances acids and bases
- has some microvilli
Define filtration
- only occurs within the corpuscle
- transport from blood in the glomerulus to the capsular space
Define reabsorption
occurs along the length of the tubule transport from tube to capillary
Define excretion
The filtrate leaves the kidneys
Define secretion
moves substances that didn't have a chance to be filtered in the glomerulus to the tubule
Define ultrafiltrate
fluid that filters into Bowman's space
What happens when too much fluid is being filtered?
If too much fluid is being filtered into the kidneys, the cells may burst and undergo apoptosis. The nephrons don't regenerate
Define glomerular filtration rate
the amount of fluid/solutes that are filtered per unit time into Bowman's space from the glomerular capillaries
Name the forces that contribute to net filtration pressure
1)
Hydrostatic pressure of Glomerular Capillaries (Pgc)
2)
Colloid Osmotic Pressure of Glomerular Capillaries (?gc)
3)
Hydrostatic Pressure of Bowman's Capsule (Pbc)
4)
Colloid Osmotic Pressure of Bowman's Capsule (?bc)
Provide the net filtration equation
(Pgc + ?bc) - (Pbc + ?gc)
What is normal net filtration?
10 mmHg
What forces act on the nephron promote filtration?
(1) Hydrostatic pressure of glomerular capillaries and (2) colloid osmotic pressure of Bowman's capsule
What forces act on the nephron inhibit filtration
(1) Colloid Osmotic Pressure of Glomerular Capillaries (?gc)
(2) Hydrostatic Pressure of Bowman's Capsule (Pbc)
Describe
hydrostatic pressure of glomerular capillaries
(Pgc)
- pressure created due to the presence and movement of fluid (blood) through the glomerular capillaries)
- generates the largest force that contributes to filtration
Describe
colloid osmotic pressure of glomerular capillaries
(?gc)
pressure created by protein in the fluid (blood) in the glomerular capillary
Describe
hydrostatic pressure of Bowman's capsule
(Pbc)
- pressure created due to the presence of fluid (filtrate) in Bowman's space
- creates back pressure
Describe
colloid osmotic pressure of Bowman's capsule
(?bc)
- pressure created by protein in the fluid (filtrate) in bowman's space
- not good
How is
filtration coefficient
determined?
It can be determined by how much surface area (size of slits between podocytes) is available for filtration and the permeability of the barriers to filtration
What happens when the slits between the podocytes increase?
GFR and flow rate increases but what is filtered doesn't change
What happens if the permeability of the basal lamina increases?
GFR and fluid flow rate increases and some proteins may filter
What happens if the size of the glomeruli pores decreases?
GFR and fluid flow rate decreases and what is being filtered doesn't change.
Describe the effect to blood flow, BP and GFR when the
afferent arteriole
CONSTRICTS
Blood flow, BP and GFR
decreases
Describe the effect to blood flow, BP and GFR when the
afferent arteriole
DILATES
blood flow, BP and GFR
increases
Describe the effect to blood flow, BP and GFR when the
efferent arteriole
CONSTRICTS
blood flow, BP, and GFR
increases
Describe the effect to blood flow, BP, and GFR when the
efferent arteriole
DILATES
blood flow, BP, and GFR
decreases
What happens when both the efferent and afferent arteriole CONSTRICT?
The effect that happens when both arterioles constrict depends on the magnitude of the constriction.
-
slight constriction
: no change
-
significant constriction
: decrease in BP, blood flow and GFR because the efferent arteriole can't over come the effec
What two mechanisms are in place to protect the kidney from significant pressure changes?
- Myogenic response
- Tubuloglomerular (TG) feedback
Describe myogenic response
distention of the afferent arterioles of nephrons, in response to increases in BP, leads to local vasoconstriction and preventing GFR from spiking
Why does myogenic response occur?
The distention of the afferent arterioles cause the opening of stretch sensitive cation channels in the smooth muscle. This muscle contracts, reducing the diameter of the afferent arteriole.
What is tubuoglomerular feedback?
The autoregulation mechanism that locally regulates GFR in response to the content of the filtrate
Describe macula densa cells
- salt detectors
- specialized cells that are part of the late part of the ascending limb of the Loop of Henle
- it twists back to come into contact with the afferent and efferent arteriole
Parts of the juxtaglomerular apparatus
macula densa cells and juxtaglomerular cells
Describe juxtaglomerular cells
- aka granular cells
- part of the afferent arteriole
- receives the signals from the macula densa cells
What do macula densa cells do when NaCl levels of the filtrate are too high?
If the macula densa cells detect that NaCl levels are too high because of a higher GFR, they release a vasoconstricter (adenosine) that causes the afferent arterioles to constrict and reduce GFR
What do macula densa cells do when GFR decreases due to lower BP?
The macula densa cells release NO, instead causing vavsodilation of the afferent arteriole
Provide an equation to determine the excretion of a substance
excretion = filtration - reabsorption + secretion
What is the best substance to measure urine?
Creatinine
is the best substance to measure urine as it is filtered and not reabsorbed. It is not the perfect substance because it is slightly secreted but its good enough.
Provide an equation for GFR
([substance x]urine x urine volume) / [substance x]plasma
Define filtered load
how much of each solute is filtered into the capsular space
Provide an equation for filtered load
filtered load = [X]plasma x GFR
How much of the filtrate is reabsorbed by the proximal tubule?
65% of the filtrate volume is reabsorbed
How much of the filtrate is reabsorbed by the loop of Henle?
20% of the filtrate volume is reabsorbed
How much of the filtrate is reabsorbed by both the distal convoluted tubule and the collect duct?
14% of the filtrate volume is reabsorbed
What is reabsorbed in the proximal tubule of the nephron?
glucose, amino acids, water, Na+, K+, and Cl-
What is reabsorbed in the descending limb of the loop of Henle?
water and minimal sodium ions
What is reabsorbed in the ascending limb of the loop of Henle?
Na+, K+, Cl-
What is reabsorbed in the distal convoluted tubule of the nephron?
Na+, K+, Cl-, Ca2+
What is reabsorbed by the collecting duct of the nephron?
Na+ and water
How does reabsorption occur?
paracellularly or transcellularly
Define paracellular transport
transport between cells
Define transcellular transport
- across the membranes through the tubule cells
- often requires transporters or channels
How does secretion occur?
occurs mostly transcellularly
Give examples of sodium trasporters
1) Sodium Channels
2) Sodium symporters
3) Sodium exchanger
4) Na+/K+ ATPase
Describe sodium channels
- protein lined pore that recognize sodium
- ENaC
Describe sodium symporters
- protein carrier
- Na+/glucose symporters (SGLT1 and SGLT2)
What does SGLT1 transport?
2 sodiums ions and 1 glucose
What does SGLT2 transport?
1 sodium ion and 1 glucose
Name a sodium exchanger
Na+/H+ (NHE3)
What helps to maintain electroneutrality when reabsorbing sodium?
- an equivalent anion must be reabsorbed
- chloride is the major anion that helps to maintain electroneutrality
- bicarbonate is occasionally used as the equivalent anion
Why is chloride preferred as sodium's anion equivalent over bicarbonate?
most of the filtered bicarbonate is reabsorbed in the proximal tubule while only 60% of the total chloride is reabsorbed
Problems with chloride transport in the nephron
- the transport into the tubule cells from the lumen is against an electrical gradient so the cell must become slightly positive for the Cl- to travel (via Na+ movement)
- transport out of the tubule cell through the basolateral membrane must be high enou
Examples of chloride transporters
- Chloride channels
- Cl- symporters
- Cl- multiporters
Name and describe a Cl- symporter
NCC
- Sodium/Chloride cotransporter
- same direction
Name and describe a chloride multiporter
NKCC2
- 2 isoforms in the body, this one is expressed in the kidney
- Na+/K+/2Cl- Cotransporter
Give examples of water transporters
- water channels, i.e. aquaporins I, II, III, IV
- paracellular water reabsorption (proximal tubule ONLY)
Name the channels/transporters found in the proximal tubule
1)
Na+/Glucose symporter
2)
Na+/amino acid symporter
3)
Na+/H+ exchanger
4)
Na+/K+ ATPase
5)
Water channel (AQI)
6)
Glucose uniporter
7)
Amino acid uniporter
8)
Paracellular H2O, K+, Cl-
Provide the location, regulation and more information on
Na+/glucose symporter
(Proximal tubule)
Location
: Luminal
Regulated
: No
Info
:
- favorable transport of Na+
- causes a glucose build up in cells
Provide the location, regulation and more information on
Na+/amino acid symporter
(Proximal tubule)
Location
: Luminal
Regulated
: No
Info
:
- moves Na+ down [ ] gradient
- AA moves against gradient
- not all AAs are recognized by this symporter
Provide the location, regulation and more information on
Na+/H+ exchanger
(Proximal tubule)
Location
: Luminal
Regulated
: Angiotensin II
Info
:
- H+ secreted to regulate blood pH by combining with bicarbonate
Provide the location, regulation and more information on
Na+/K+ ATPase
(Proximal tubule)
Location
: Basolateral
Regulated
: Angiotensin II
Info
:
- primary active transporter
- maintains low [Na+]
Provide the location, regulation and more information on
water channel AQI on luminal membrane
(Proximal tubule)
Location
: Luminal
Regulated
: No
Info
:
- Water follows the increase of [solute] i.e. osmosis
Provide the location, regulation and more information on
water channels AQI on basolateral membrane
(Proximal tubule)
Location
: basolateral
Regulated
: No
Info
:
- because other solutes have moved out of the cell
Provide the location, regulation and more information on
glucose uniporter
(Proximal tubule)
Location
: Basolateral
Regulated
: No
Info
: favorable gradient
Provide the location, regulation and more information on
amino acid uniporter
(Proximal tubule)
Location
: Basolateral
Regulated
: No
Info
: favorable gradient
Provide the location, regulation and more information on
paracellular transport
(Proximal tubule)
Location
: N/A
Regulated
: No
Info
:
- favorable [ ] gradient of interstitial space and filtrate (H2O and K+)
- Cl- moves because interstitial space is becoming more positive
Describe
diabetes mellitus
- ?'d levels of glucose in blood
- ?'d load of filtered glucose cannot be adequately reabsorbed by the
Na+/glucose symporters
s* found in the tubule epithelial cells
- osmotic diuresis occurs
Define osmotic diuresis
An increase in urine production due to less water being reabsorbed due to osmosis
Describe non-renal symptoms of diabetes mellitus
- ketoacidosis: body believes it is starving
- confusion, headache, fatigue, diuretic neuropathy
Name the channels/transporters found in the
descending limb of the loop of Henle
1)
Water channel (AQ I)
2)
Na+ channel
3)
Na+/K+ ATPase
Provide the location, regulation and more information on
AQ I channels
(Descending limb of the loop of Henle)
Location
: luminal and basolateral membrane
Regulated
: No
Info
: following high concentration of ions in the interstitial space
Provide the location, regulation and more information on
Na+ channel
(Descending limb of the loop of Henle)
Location
: Luminal
Regulated
: No
Info
: very little transport
Provide the location, regulation and more information on
Na+/K+ ATPase
(Descending limb of the loop of Henle)
Location
: basolateral
Regulated
: No
Info
: n/a
Name the channels/transporters found at the thick ascending limb of the loop of Henle
1)
Na+ channel
2)
Na+/2Cl-/K+ symporters (ion multiplier)
3)
K+ channel (leak channel)
4)
K+/Cl- symporter
5)
Na+/K+ ATPase
6)
Paracellular Na+
7)
Cl- channel
Provide the location, regulation and more information on
Na+ channel
(Ascending limb of the loop of Henle)
Location
: Luminal
Regulation
: No
Info
: Reabsorbs Na+, follows [ ] gradient
Provide the location, regulation and more information on
Na+/2Cl-/K+ symporters
(Ascending limb of the loop of Henle)
Location
: luminal
Regulation
: No
Info
:
- NKCC2 transporter
- 4 ions are transported with 1 conformational change
- only Na+ transport is favorable, driving the motion
Provide the location, regulation and more information on
K+ channel
(Ascending limb of the loop of Henle)
Location
: luminal
Regulation
: No
Info
: transports out K+ that is transported in by the ion multiplier to allow it to continue moving its ions
Provide the location, regulation and more information on
K+/Cl- symporter
(Ascending limb of the loop of Henle)
Location
: Basolateral
Regulation
: No
Info
: K+ is favorable
Provide the location, regulation and more information on
Na+/K+ ATPase
(Ascending limb of the loop of Henle)
Location
: basolateral
Regulation
: N/A
Info
: N/A
Provide more information on
paracellular Na+
(Ascending limb of the loop of Henle)
negative charge building up in interstitum allows Na+ transport by these means
Provide the location, regulation and more information on
Cl- channel
(Ascending limb of the loop of Henle)
Location
: basolateral
Regulation
: NO
Info
:
- Cl- can move because of a build up inside of cell can overcome the [Cl-] of the interstitial tissue
- there is also electrical gradient favoring
Name the channel/transport in the distal convoluted tubule
1)
Na+ channel
2)
Na+/Cl- symporter
3)
Na+/K+ ATPase
4)
Ca+ channel
5)
K+/Cl- symport
6)
Na+/Ca++ antiporter
Provide the location, regulation and more information on
Na+ channel
(distal convoluted tubule)
Location
: luminal
Regulation
: No
Info
: simple diffusion
Provide the location, regulation and more information on
Na+/Cl- symporter
(distal convoluted tubule)
Location
: luminal
Regulation
: No
Info
: reabsorbs Cl- using Na+ gradient
Provide the location, regulation and more information on
Na+/K+ ATPase
(distal convoluted tubule)
Location
: basolateral
Regulation
: No
Info
: maintains [ ] gradient
Provide the location, regulation and more information on
Ca++ channel
(distal convoluted tubule)
Location
: luminal
Regulation
: no
Info
: n/a
Provide the location, regulation and more information on
K+/Cl- symport
(distal convoluted tubule)
Location
: basolateral
Regulation
: No
Info
: 1:1 NaCl ratio so extra Cl- channel is not needed
Provide the location, regulation and more information on
Na+/Ca++ antiporter
(distal convoluted tubule)
Location
: basolateral
Regulation
: parathyroid hormone
Info
: N/A
Name the channel/transporters in the principle cells of the collecting duct
1)
AQ II
2)
AQ III and IV
3)
Na+ channel
4)
K+ channel
5)
Na+/K+ ATPase
Provide the location, regulation and more information on
AQ II
(collecting duct)
Location
: luminal
Regulation
: Anti-Diuretic Hormone
Info
:
- can either be within membrane or endocytosed
- ADH present: AQ II in membrane
Provide the location, regulation and more information on
AQ III & IV
(collecting duct)
Location
: basolateral
Regulation
: No
Info
: N/a
Provide the location, regulation and more information on
Na+ channel
(collecting duct)
Location
: luminal
Regulation
: Aldosterone
Info
: ENaC
Provide the location, regulation and more information on
K+ channel
(collecting duct)
Location
: luminal
Regulation
: aldosterone
Info
: secretions allows a safety mechanism for when the individual experiences hyperkalemia
Provide the location, regulation and more information on
Na+/K+ ATPase
(collecting duct)
Location
: Basolateral
Regulation
: Aldosterone
Info
: maintains [ ] gradient
Define
hyperuricemia
a condition defined by an increase in uric acid (aka rate) in the blood
What causes gout and kidney stones?
hyperuricemia, more specifically, crystalization of uric acid in joints (
gout
) and kidney tubules/ureter/urther (
kidney stones
)
Define gout
swelling of the joints, especially the smaller ones, due to the deposition of crystalize uric acid
Define kidney stones
painful condition in which crystallized uric acid gets stuck in the tubules, ureter or urther
Common symptoms of kidney stones
pain and decreased urine output
Name 2 hormone systems that regulate Na+ levels
1)
Renin-Angiotensin-Aldosterone System
(RAAS) - sodium levels are low
2)
Atrial Natriuretic Peptide
(ANP) - sodium levels are high
Describe
Renin
an enzyme secreted into the blood stream by JG cells when there are low levels of sodium in the body, acts on the inactive angiotensin to convert it to
angiotensin I
(10 AA)
Describe Angiotensinogen
- constitutively produced by the liever
- 452 AAs long
- secreted into the blood stream
- not hormonally active
Describe Angiotensin I
- converted from angiotensinogen via renin
- 10 AAs
- not hormonally active
Describe ACE
- angiotensin convering enzyme
- produced by all endothelial cells
- highest in the pulmonary capillary bed
- converts angiotensin I into angiotensin II (8 AAs)
What makes Angiotensin II?
cleavage of angiotensinogen to angiotensin I and then to angiotensin II
Hormone properties of angiotensin II
peptide hormone, released into the blood stream when triggered
Stimulus for angiotensin II
renin release
General effect of Angiotensin II
causes an increase in sodium reabsorption in the proximal tubule
How does Angiotensin II affect Na+ reabsorption in the proximal tubule?
- ? activity of the Na+/H+ exchanger
- ? activity of the Na+/K+ ATPase
- Constrict both the afferent efferent arteriole, ?ing GFR and [Na+] filtered load
Why does slowing down fluid in the tubule increase Na+ reabsorption?
This allows more time for Na+ to be reabsorbed
Describe how angiotensin II carries out its action
Angiotensin II can be filtered and its receptors are on both the luminal and basolateral membranes. When Angiotensin II interacts with their receptors, the receptors produce local changes at their respective membranes
What is aldosterone made by?
the adrenal glands
What are the hormone properties of aldosterone?
steroid hormone
What is the stimulus of aldosterone?
- angiotensin II
- high potassium levels
- adrenal corticotropin hormone (ACTH)
General action of aldosterone
causes an increase in Na+ reabsorption in the collecting duct
How does Aldosterone increase Na+ reabsorption in the collecting duct?
- ? # of Na+ and K+ channels in the luminal membrane (translocation)
- ? activity of Na+/K+ ATPase (basolateral)
- ? expression level of both Na+ channels and Na+/K+ ATPases
How does binding of aldosterone affect Na+ reabsorption?
binding of aldosterone increases Na+ channels (reabsorption) and K+ channels (secretion) in the luminal membrane
Where are baroreceptors located?
- in the carotid sinus and special neural reflex directly to juxtaglomerular cells ? sympathetic
- at juxtaglomerular cells (aka intrarenal baroreceptors) ? afferent arteriole stretching
What stimulates JG cells to release renin?
- low intrarenal pressure of the afferent arterioles
- sympathetic innervation from carotid sinus (low BP)
- macular densa cells (Low Na+ in filtrate detected)
How do macula densa cells detect NaCl content?
macula densa cells detect NaCl content of the lumen through the activity of the Na-K-2Cl multiporter
Response of macula densa cells to high NaCl content in relation to GFR
- secrete ATP
- ATP is converted to adenosine extracellularly
- decrease local GFR
How does adenosine function in the kidneys?
acts as a vasoconstrictor that decreases local GFR
Response of macula densa cells to low NaCl content in relation to GFR
- release of Nitric Oxide (NO)
- increase in GFR
effect of NO in the kidneys
- NO is a vasodilator
- has a greater effect on the afferent arteriole and results in an ? in GFR
How do macula densa cells respond to high NaCl? (in relation to renin)
ATP and adenosine are released by macula densa cells and they bind to purinergic receptors on the JG cells. This causes a
decrease
in renin release
How do macula densa cells respond to low NaCl? (in relation to renin)
Low NaCl in the tubular filtrate cause macula densa cells to release
prostaglandins
which stimulate JG cells to
produce
and
release renin
How do macula densa cells respond to high tubular fluid flow?
- macula densa cells release ATP leading to the production of adenosine
- vasoconstriction
- decrease in GFR slowing down the fluid flow rate in the local tubule
How do macula densa cells respond to low tubular fluid flow?
- macula densa cells release NO as well as
prostaglandins
- ? GFR and ? fluid flow rate in the local nephron tubule
How do macula densa cells detect tubular flow?
Macula densa cells have
cilia
that bend less with decreased tubular flow and bend more with increased tubular flow
What is atrial natriuretic peptide made by?
cardiac atrial cells
What are the hormone properties of atrial natriuretic peptide?
peptide hormone, released into the blood when triggered
What is the stimulus of atrial natriuretic peptide?
high blood pressure
What are the sensors for atrial natriuretic peptide?
stretch receptors (located in
both
atrias)
General action of atrial natriuretic peptide
inhibit Na+ reabsorption
How does atrial natriuretic peptide inhibit Na+ reabsorption?
- ANP inhibits aldosterone secretion by the adrenal gland
- causes
dilation
of the
afferent arteriole
to ?GFR, ?ing flow throughout the tubule leading to ? Na+ excretion
What does high body levels of Na+ result in?
- a global release of ANP but also a release of adenosine
- effect of ANP outweighs the local effect of adenosine, especially in the nephron
What makes anti-diuretic hormone?
neuroendocrine cells in the hypothalamus
Where is anti-diuretic hormone stored?
posterior pituitary gland
What are the hormone properties of anti-diuretic hormone?
peptide hormone, released into the blood when triggered
What is the stimulus of anti-diuretic hormone?
- high plasma osmolarity
- low ECF volume (resulting in low BP)
- Angiotensin II
What are the sensors of anti-diuretic hormone
- osmoreceptors
- baroreceptors
Describe the relationship between osmoreceptors and ADH
increase in plasma osmolarity causes osmoreceptors to shrink in volume, triggering ADH release
Describe the relationship between baroreceptors and ADH
if ECF volume ?, causes the release of ADH by ?'d APs sent to the hypothalamus via the baroreceptors
Describe the action of ADH
?s the # of AQ II channels on the luminal membrane of the collecting duct (relocation of existing channels)
Where are ADH receptors located?
on the basolateral membrane
Describe how an increase in plasma osmolarity stimulates ADH release
An increase in osmolarity of ECF will cause the osmoreceptors near the 3rd ventricle to shrivel in response. The activity of neuroendocrine cells increases and an increase in ADH secretion into the blood increases. Water reabsorption increases and water e
Describe how a decrease in blood volume stimulates ADH release
A decrease in blood volume causes a decrease in MAP. Both will cause baroreceptors to respond by decreasing the amount of APs they fired. The activity of the neuroendocrine cells increases and more ADH is secreted. Water reabsorption increases and water e
What happens if both osmoreceptors and baroreceptors are stimulated?
A increase in plasma osmolarity and a decrease in plasma volume will cause a significant amount of ADH to be released into the blood stream. The converse is true, causing inhibition of ADH release.
What happens to ADH release when there is a decrease in both plasma osmolarity and blood volume under normal physiological conditions?
Under normal physiological conditions, the response to the osmoreceptors is deemed to be more improtant than the baroreceptors. Therefore, less ADH is released.
What happens to ADH release when there is a decrease in both plasma osmolarity and blood volume under severe conditions, such as hemorrhage?
The need to secrete ADH in response to the baroreceptors and volumereceptors (in atria) overcomes the need to inhibit ADH secretion in response to the osmolarities
What is the osmolarity of filtrate in the proximal tubule?
Approximately 300 mOsm because both ions and H2O are being reabsorbed
What happens to filtrate osmolarity in the descending limb of the loop of Henle?
Since only H2O is reabsorbed, filtrate osmolarity increases, a maximum concetration of ~1400 mOsm
What happens to filtrate osmolarity in the ascending limb of the loop of Henle?
Since only ions are reabsorbed, filtrate osmolarity decreases. An electrochemical gradient allows the ions to leak paracellularly.
What happens to filtrate osmolarity in the distal convoluted tubule?
The filtrate is most dilute here, ~100 mOsm.
What is the maximum difference between the filtrate and medulla?
200 mOsm
Describe urine osmolarity in the collecting duct
- If H2O can't be reabsorbed in the collecting duct, the urine will be very dilute (~100 mOsm) and at very large volumes.
- Maximal amount of ADH will lead to maximal H2O reabsorption, leading to urine with osmolarity of 1400 mOsm
Define Diuresis
An increase in urine production
Define natriuresis
an increase in Na+ excretion
Name examples of diuretics
1) Ethanol
2) AVP receptor antagonist
3) NKCC transporter antagonist
Describe Ethanol
(Diuretics)
- inhibits release of ADH
- causes ? in urine production
Describe AVP receptor antagonist)
(Diuretics)
- prevents ADH from binding and therefore preventing water reabsorption
- good for high BP and heart failure
Describe NKCC transporter antagonist
(Diuretics)
- ?s renal medulla osmolarity
- ? Na reabsorption, affecting medulla osmolarity
Describe
diabetes insipidus
- affects the ability of ADH to stimulate water reabsorption in the collecting duct of nephrons
- less water being reabsorbed leads to a much higher urine production, causing severe dehydration
What does it mean for diabetes insipidus to be neurogenic?
- failure to release ADH
- administer synthetic ADH to treat
What does it mean for diabetes insipidus to be nephrogenic
- failure of collecting duct cells to respond to ADH
- treat symptoms as necessary
Normal blood pH
~ 7.2 - 7.4
How do the kidneys help to maintain pH?
1) excrete excess H+ or HCO3-
2) Reabsorb most of the HCO3- in the proximal tubule
3) Create new bicarbonate ions by renal tubule cells
Name sources of acids in the body
1) Food
2) Metabolic intermediates
3) Lactic acid created by anaerobic metabolism
4) Production of CO2 by aerobic respiration
Food
(acid source)
acidic fruits, amino acids (ones that contain sulfur), fatty acids, etc.
Metabolic intermediates
(acid source)
lactate, pyruvate, citric acid cycle products
Production of CO2 by aerobic respiration
(acid source)
- CO2 combines with H2O to produce ccarbonic acid that dissociates int H+ and HCO3-
- biggest source of acid in the body
Name sources of bases in the body
1) Food
- some fruits and vegetables metabolize to HCO3-
Carbonic anhydrase
- enzyme that catalyzes the forward and reverse reaction of bicarbonate synthesis
- depending on the cell, it can be found in either the luminal membrane, basolateral membrane or cytosol
What must happen before HCO3- is reabsorbed?
It must first be converted to CO2. This is accomplished by letting H+ interact with the HCO3- to convert it to CO2 and H2O. Once the CO2 has diffused into the cells, it will react with H2O and be catalyzed by carbonic anhydrase back into HCO3- and H+
How does HCO3- get reabsorbed into the capillaries?
It is transported across the basolateral membrane of the tubule cells via a Na+/HCO3- symporter. The gradient of the HCO3- is driving the transport, NOT the Na+ gradient
What collecting duct cells secrete H+ ions into the lumen?
Type A intercalated cells
Describe the transporters of Type A intercalated cells of the collecting duct.
Luminal membrane transporters
- H+ ATPase
- H+/K+ ATPase
- translocated to the membrane
- require energy
Basolateral membrane transporters
- HCO3-/Cl- antiporter
- permanently embedded in the membrane
- driven by Cl- [ ] gradient
What activates Type A intercalated cells of the collecting duct?
the binding of H+ to receptors on the cells' basolateral membrane
What are some conditions associated with an increase in blood [H+]?
- acidosis
- hyperkalemia (high blood [K+])
What are the collecting duct cells that secrete HCO3- into the lumen?
Type B intercalated cells
Describe the transporters in the type B intercalated cells of the collecting duct
Luminal membrane transporters
- HCO3-/Cl- antiporter
- translocated into the membrane
- driven by Cl- [ ] gradient
Basolateral membrane transporters
- H+ ATPase
- H+/K+ ATPase antiport
- require energy
What are conditions commonly associated with increased blood pH?
- alkalosis
- hypokalemia
Name 4 causes of acid/base disturbances
1) Metabolic Acidosis
2) Respiratory Acidosis
3) Metabolic Alkalosis
4) Respiratory Alkalosis
Describe metabolic acidosis
- due to excessive breakdown of fats or certain amino acids
- can be caused by excessive ingestion of aspirin
- can be caused by ingestion of methanol and antifreeze
- increases H+ load
Causes of respiratory acidosis
- hypoventilation
- respiratory depression due to drugs (including alcohol)
- airway resistance due to asthma
- diseases that affect gas exchange in the lungs (e.g. fibrosis and muscle weakness from muscular dystrophy)
Causes of Metabolic Alkalosis
- excessive loss of H+ due to excessive vomiting
- excessive ingestion of bicarbonate-containing antacids
Causes of respiratory alkalosis
results from too much CO2 being expelled through the lungs via hyperventilation
Functions of the kidneys
1)
Regulates ionic compositions of blood
2)
Regulates blood pH
3)
Regulates blood volume
4)
Regulates blood pressure
5)
Maintains blood osmolarity
6)
Produces hormones
7)
Regulates blood glucose levels
8)
Excretes wastes and foreign substances
Why is it important for the kidneys to regulate blood pH?
Because proteins fold at specific pH
How do kidneys relate to blood volume?
- works with the heart
- Higher BV, kidneys excrete more water
- Lower BV, kidneys excrete less water
How do kidneys relate to blood pressure?
- The kidneys respond to baroreceptors and volume receptors
- works with the heart
How do kidneys relate to maintaining blood osmolarity?
- closely linked to regulating ionic compositions of blood
- normal osmolarity ~300 mOsm (all solutes dissolved in blood, not just ions)
What hormones do the kidneys produce?
- produces erythropoietin
- converts Vitamin D into
calcitrol
(active form)
How do kidneys help to regulate blood glucose levels?
the kidneys can carry out gluconeogenesis
What are some of the substances that the kidneys excrete?
- urea
- uric acid
- creatinine
- urobilin (from break down of hemoglobin)
Where are there kidneys located?
The 2 kidneys are located on either side of the spine, posterior to the abdomen, ~11th/12th rib. Therefore, the kidneys are located in the
retroperitoneal cavity
.
What is the renal pelvis?
where urine is collected
What are the calyces?
Pyramid-like structures at the bottom of the medulla that funnels the processed urine into the renal pelvis
How much of the cardiac output d the kidneys receive (each)?
20% of the cardiac output each
Define nephron
the functional unit of the kidney
How many nephrons do each kidney have?
~1 million nephrons each
Name the 2 basic structures of the nephron
- Renal corpuscle
- tubule
Main responsibility of renal corpuscle
filter blood
General responsibility of the tubule
processes the filtered fluid
Difference between filtrate and urine?
filtrate is in the nephron and urine in the after collecting duct
Name the 2 types of nephrons in the kidneys
- Cortical Nephron
- Juxtamedullary Nephron
Describe Cortical Nephrons
- 80% of nephrons in humans
- shorter loop of Henle, mostly in the cortex
- as a
peritubular capillary bed
Describe Juxtamedullary nephron
- long loop of Henle, mostly in medulla
- Vasa recta capillary bed
Describe the vasa recta capillary bed of the juxtamedullary nephron
- parallel with the loop of Henle
- helps maintain the increasing osmolarity of the medulla of the kidney
Where are the renal corpuscles located?
The renal corpuscles of all nephrons are located in the cortex of the kidney
Name the two main structures of the renal corpuscle
- Bowman's capsule
- glomerulus
Describe the Bowman's capsule
- fluid filled hollow ball-like structure
- surrounds glomerulus
- made of epithelial cells that is continuous with the proximal tubule
Describe the glomerulus
- specialized structure of "leaky" capillaries due to having many fenestrae (pores)
- endothelium is fused with the epithelium of Bowman's capsule
Describe the purpose of the basal lamina in the glomerulus
- basal lamina is the layer of ECM connecting the endothelium and the epithelium of Bowman's capsule
- serves as a rough sieve for filtering
- excludes nearly all plasma proteins
What are podocytes?
They are specialized epithelial cells that acts as a third filtering component of the renal corpuscle.
Describe the appearance of podocytes.
- they have long foot-like processes that interlace with one another around the glomerulus capillaries
- leaves narrow sllits that help to control the rate of fluid filtration into Bowman' capsule
- damage can lead to an increase filtration of fluid
What is urinalysis?
Uses urine test strips that use colorimetric reactions to indicate the presence or absence of substances in the urine.
What should not be filtered into the urine?
- leukocytes
- nitrites
- protein
- haemoglobin
- ketones
- bilirubin
- glucose
What is normal urine pH?
6
What is specific gravity?
It looks at the concentration of urine
What does high specific gravity indicate?
A higher specific gravity indicates more concentrated urine
and that the individual is dehydrated.
Describe the epithelial cell type in proximal tubule
consists ONLY of
simple columnar epithelium
with microvilli and many mitochondria
Describe the epithelial cell type(s) in the descending limb of the loop of Henle
consists ONLY of
simple squamous epithelium
with some microvilli but they are not as metabolically active
Describe the epithelial cell type(s) in the collecting duct
It has a mixed population of cuboidal cells:
-
principal cells
-
Intercalated cells
Describe the principal cells of the collecting duct
- highest #
- reabsorbs
- responsive to hormone
- metabolically active
Describe the intercalated cells of the collecting duct
- balances acids and bases
- has some microvilli
Define filtration
- only occurs within the corpuscle
- transport from blood in the glomerulus to the capsular space
Define reabsorption
occurs along the length of the tubule transport from tube to capillary
Define excretion
The filtrate leaves the kidneys
Define secretion
moves substances that didn't have a chance to be filtered in the glomerulus to the tubule
Define ultrafiltrate
fluid that filters into Bowman's space
What happens when too much fluid is being filtered?
If too much fluid is being filtered into the kidneys, the cells may burst and undergo apoptosis. The nephrons don't regenerate
Define glomerular filtration rate
the amount of fluid/solutes that are filtered per unit time into Bowman's space from the glomerular capillaries
Name the forces that contribute to net filtration pressure
1)
Hydrostatic pressure of Glomerular Capillaries (Pgc)
2)
Colloid Osmotic Pressure of Glomerular Capillaries (?gc)
3)
Hydrostatic Pressure of Bowman's Capsule (Pbc)
4)
Colloid Osmotic Pressure of Bowman's Capsule (?bc)
Provide the net filtration equation
(Pgc + ?bc) - (Pbc + ?gc)
What is normal net filtration?
10 mmHg
What forces act on the nephron promote filtration?
(1) Hydrostatic pressure of glomerular capillaries and (2) colloid osmotic pressure of Bowman's capsule
What forces act on the nephron inhibit filtration
(1) Colloid Osmotic Pressure of Glomerular Capillaries (?gc)
(2) Hydrostatic Pressure of Bowman's Capsule (Pbc)
Describe
hydrostatic pressure of glomerular capillaries
(Pgc)
- pressure created due to the presence and movement of fluid (blood) through the glomerular capillaries)
- generates the largest force that contributes to filtration
Describe
colloid osmotic pressure of glomerular capillaries
(?gc)
pressure created by protein in the fluid (blood) in the glomerular capillary
Describe
hydrostatic pressure of Bowman's capsule
(Pbc)
- pressure created due to the presence of fluid (filtrate) in Bowman's space
- creates back pressure
Describe
colloid osmotic pressure of Bowman's capsule
(?bc)
- pressure created by protein in the fluid (filtrate) in bowman's space
- not good
How is
filtration coefficient
determined?
It can be determined by how much surface area (size of slits between podocytes) is available for filtration and the permeability of the barriers to filtration
What happens when the slits between the podocytes increase?
GFR and flow rate increases but what is filtered doesn't change
What happens if the permeability of the basal lamina increases?
GFR and fluid flow rate increases and some proteins may filter
What happens if the size of the glomeruli pores decreases?
GFR and fluid flow rate decreases and what is being filtered doesn't change.
Describe the effect to blood flow, BP and GFR when the
afferent arteriole
CONSTRICTS
Blood flow, BP and GFR
decreases
Describe the effect to blood flow, BP and GFR when the
afferent arteriole
DILATES
blood flow, BP and GFR
increases
Describe the effect to blood flow, BP and GFR when the
efferent arteriole
CONSTRICTS
blood flow, BP, and GFR
increases
Describe the effect to blood flow, BP, and GFR when the
efferent arteriole
DILATES
blood flow, BP, and GFR
decreases
What happens when both the efferent and afferent arteriole CONSTRICT?
The effect that happens when both arterioles constrict depends on the magnitude of the constriction.
-
slight constriction
: no change
-
significant constriction
: decrease in BP, blood flow and GFR because the efferent arteriole can't over come the effec
What two mechanisms are in place to protect the kidney from significant pressure changes?
- Myogenic response
- Tubuloglomerular (TG) feedback
Describe myogenic response
distention of the afferent arterioles of nephrons, in response to increases in BP, leads to local vasoconstriction and preventing GFR from spiking
Why does myogenic response occur?
The distention of the afferent arterioles cause the opening of stretch sensitive cation channels in the smooth muscle. This muscle contracts, reducing the diameter of the afferent arteriole.
What is tubuoglomerular feedback?
The autoregulation mechanism that locally regulates GFR in response to the content of the filtrate
Describe macula densa cells
- salt detectors
- specialized cells that are part of the late part of the ascending limb of the Loop of Henle
- it twists back to come into contact with the afferent and efferent arteriole
Parts of the juxtaglomerular apparatus
macula densa cells and juxtaglomerular cells
Describe juxtaglomerular cells
- aka granular cells
- part of the afferent arteriole
- receives the signals from the macula densa cells
What do macula densa cells do when NaCl levels of the filtrate are too high?
If the macula densa cells detect that NaCl levels are too high because of a higher GFR, they release a vasoconstricter (adenosine) that causes the afferent arterioles to constrict and reduce GFR
What do macula densa cells do when GFR decreases due to lower BP?
The macula densa cells release NO, instead causing vavsodilation of the afferent arteriole
Provide an equation to determine the excretion of a substance
excretion = filtration - reabsorption + secretion
What is the best substance to measure urine?
Creatinine
is the best substance to measure urine as it is filtered and not reabsorbed. It is not the perfect substance because it is slightly secreted but its good enough.
Provide an equation for GFR
([substance x]urine x urine volume) / [substance x]plasma
Define filtered load
how much of each solute is filtered into the capsular space
Provide an equation for filtered load
filtered load = [X]plasma x GFR
How much of the filtrate is reabsorbed by the proximal tubule?
65% of the filtrate volume is reabsorbed
How much of the filtrate is reabsorbed by the loop of Henle?
20% of the filtrate volume is reabsorbed
How much of the filtrate is reabsorbed by both the distal convoluted tubule and the collect duct?
14% of the filtrate volume is reabsorbed
What is reabsorbed in the proximal tubule of the nephron?
glucose, amino acids, water, Na+, K+, and Cl-
What is reabsorbed in the descending limb of the loop of Henle?
water and minimal sodium ions
What is reabsorbed in the ascending limb of the loop of Henle?
Na+, K+, Cl-
What is reabsorbed in the distal convoluted tubule of the nephron?
Na+, K+, Cl-, Ca2+
What is reabsorbed by the collecting duct of the nephron?
Na+ and water
How does reabsorption occur?
paracellularly or transcellularly
Define paracellular transport
transport between cells
Define transcellular transport
- across the membranes through the tubule cells
- often requires transporters or channels
How does secretion occur?
occurs mostly transcellularly
Give examples of sodium trasporters
1) Sodium Channels
2) Sodium symporters
3) Sodium exchanger
4) Na+/K+ ATPase
Describe sodium channels
- protein lined pore that recognize sodium
- ENaC
Describe sodium symporters
- protein carrier
- Na+/glucose symporters (SGLT1 and SGLT2)
What does SGLT1 transport?
2 sodiums ions and 1 glucose
What does SGLT2 transport?
1 sodium ion and 1 glucose
Name a sodium exchanger
Na+/H+ (NHE3)
What helps to maintain electroneutrality when reabsorbing sodium?
- an equivalent anion must be reabsorbed
- chloride is the major anion that helps to maintain electroneutrality
- bicarbonate is occasionally used as the equivalent anion
Why is chloride preferred as sodium's anion equivalent over bicarbonate?
most of the filtered bicarbonate is reabsorbed in the proximal tubule while only 60% of the total chloride is reabsorbed
Problems with chloride transport in the nephron
- the transport into the tubule cells from the lumen is against an electrical gradient so the cell must become slightly positive for the Cl- to travel (via Na+ movement)
- transport out of the tubule cell through the basolateral membrane must be high enou
Examples of chloride transporters
- Chloride channels
- Cl- symporters
- Cl- multiporters
Name and describe a Cl- symporter
NCC
- Sodium/Chloride cotransporter
- same direction
Name and describe a chloride multiporter
NKCC2
- 2 isoforms in the body, this one is expressed in the kidney
- Na+/K+/2Cl- Cotransporter
Give examples of water transporters
- water channels, i.e. aquaporins I, II, III, IV
- paracellular water reabsorption (proximal tubule ONLY)
Name the channels/transporters found in the proximal tubule
1)
Na+/Glucose symporter
2)
Na+/amino acid symporter
3)
Na+/H+ exchanger
4)
Na+/K+ ATPase
5)
Water channel (AQI)
6)
Glucose uniporter
7)
Amino acid uniporter
8)
Paracellular H2O, K+, Cl-
Provide the location, regulation and more information on
Na+/glucose symporter
(Proximal tubule)
Location
: Luminal
Regulated
: No
Info
:
- favorable transport of Na+
- causes a glucose build up in cells
Provide the location, regulation and more information on
Na+/amino acid symporter
(Proximal tubule)
Location
: Luminal
Regulated
: No
Info
:
- moves Na+ down [ ] gradient
- AA moves against gradient
- not all AAs are recognized by this symporter
Provide the location, regulation and more information on
Na+/H+ exchanger
(Proximal tubule)
Location
: Luminal
Regulated
: Angiotensin II
Info
:
- H+ secreted to regulate blood pH by combining with bicarbonate
Provide the location, regulation and more information on
Na+/K+ ATPase
(Proximal tubule)
Location
: Basolateral
Regulated
: Angiotensin II
Info
:
- primary active transporter
- maintains low [Na+]
Provide the location, regulation and more information on
water channel AQI on luminal membrane
(Proximal tubule)
Location
: Luminal
Regulated
: No
Info
:
- Water follows the increase of [solute] i.e. osmosis
Provide the location, regulation and more information on
water channels AQI on basolateral membrane
(Proximal tubule)
Location
: basolateral
Regulated
: No
Info
:
- because other solutes have moved out of the cell
Provide the location, regulation and more information on
glucose uniporter
(Proximal tubule)
Location
: Basolateral
Regulated
: No
Info
: favorable gradient
Provide the location, regulation and more information on
amino acid uniporter
(Proximal tubule)
Location
: Basolateral
Regulated
: No
Info
: favorable gradient
Provide the location, regulation and more information on
paracellular transport
(Proximal tubule)
Location
: N/A
Regulated
: No
Info
:
- favorable [ ] gradient of interstitial space and filtrate (H2O and K+)
- Cl- moves because interstitial space is becoming more positive
Describe
diabetes mellitus
- ?'d levels of glucose in blood
- ?'d load of filtered glucose cannot be adequately reabsorbed by the
Na+/glucose symporters
s* found in the tubule epithelial cells
- osmotic diuresis occurs
Define osmotic diuresis
An increase in urine production due to less water being reabsorbed due to osmosis
Describe non-renal symptoms of diabetes mellitus
- ketoacidosis: body believes it is starving
- confusion, headache, fatigue, diuretic neuropathy
Name the channels/transporters found in the
descending limb of the loop of Henle
1)
Water channel (AQ I)
2)
Na+ channel
3)
Na+/K+ ATPase
Provide the location, regulation and more information on
AQ I channels
(Descending limb of the loop of Henle)
Location
: luminal and basolateral membrane
Regulated
: No
Info
: following high concentration of ions in the interstitial space
Provide the location, regulation and more information on
Na+ channel
(Descending limb of the loop of Henle)
Location
: Luminal
Regulated
: No
Info
: very little transport
Provide the location, regulation and more information on
Na+/K+ ATPase
(Descending limb of the loop of Henle)
Location
: basolateral
Regulated
: No
Info
: n/a
Name the channels/transporters found at the thick ascending limb of the loop of Henle
1)
Na+ channel
2)
Na+/2Cl-/K+ symporters (ion multiplier)
3)
K+ channel (leak channel)
4)
K+/Cl- symporter
5)
Na+/K+ ATPase
6)
Paracellular Na+
7)
Cl- channel
Provide the location, regulation and more information on
Na+ channel
(Ascending limb of the loop of Henle)
Location
: Luminal
Regulation
: No
Info
: Reabsorbs Na+, follows [ ] gradient
Provide the location, regulation and more information on
Na+/2Cl-/K+ symporters
(Ascending limb of the loop of Henle)
Location
: luminal
Regulation
: No
Info
:
- NKCC2 transporter
- 4 ions are transported with 1 conformational change
- only Na+ transport is favorable, driving the motion
Provide the location, regulation and more information on
K+ channel
(Ascending limb of the loop of Henle)
Location
: luminal
Regulation
: No
Info
: transports out K+ that is transported in by the ion multiplier to allow it to continue moving its ions
Provide the location, regulation and more information on
K+/Cl- symporter
(Ascending limb of the loop of Henle)
Location
: Basolateral
Regulation
: No
Info
: K+ is favorable
Provide the location, regulation and more information on
Na+/K+ ATPase
(Ascending limb of the loop of Henle)
Location
: basolateral
Regulation
: N/A
Info
: N/A
Provide more information on
paracellular Na+
(Ascending limb of the loop of Henle)
negative charge building up in interstitum allows Na+ transport by these means
Provide the location, regulation and more information on
Cl- channel
(Ascending limb of the loop of Henle)
Location
: basolateral
Regulation
: NO
Info
:
- Cl- can move because of a build up inside of cell can overcome the [Cl-] of the interstitial tissue
- there is also electrical gradient favoring
Name the channel/transport in the distal convoluted tubule
1)
Na+ channel
2)
Na+/Cl- symporter
3)
Na+/K+ ATPase
4)
Ca+ channel
5)
K+/Cl- symport
6)
Na+/Ca++ antiporter
Provide the location, regulation and more information on
Na+ channel
(distal convoluted tubule)
Location
: luminal
Regulation
: No
Info
: simple diffusion
Provide the location, regulation and more information on
Na+/Cl- symporter
(distal convoluted tubule)
Location
: luminal
Regulation
: No
Info
: reabsorbs Cl- using Na+ gradient
Provide the location, regulation and more information on
Na+/K+ ATPase
(distal convoluted tubule)
Location
: basolateral
Regulation
: No
Info
: maintains [ ] gradient
Provide the location, regulation and more information on
Ca++ channel
(distal convoluted tubule)
Location
: luminal
Regulation
: no
Info
: n/a
Provide the location, regulation and more information on
K+/Cl- symport
(distal convoluted tubule)
Location
: basolateral
Regulation
: No
Info
: 1:1 NaCl ratio so extra Cl- channel is not needed
Provide the location, regulation and more information on
Na+/Ca++ antiporter
(distal convoluted tubule)
Location
: basolateral
Regulation
: parathyroid hormone
Info
: N/A
Name the channel/transporters in the principle cells of the collecting duct
1)
AQ II
2)
AQ III and IV
3)
Na+ channel
4)
K+ channel
5)
Na+/K+ ATPase
Provide the location, regulation and more information on
AQ II
(collecting duct)
Location
: luminal
Regulation
: Anti-Diuretic Hormone
Info
:
- can either be within membrane or endocytosed
- ADH present: AQ II in membrane
Provide the location, regulation and more information on
AQ III & IV
(collecting duct)
Location
: basolateral
Regulation
: No
Info
: N/a
Provide the location, regulation and more information on
Na+ channel
(collecting duct)
Location
: luminal
Regulation
: Aldosterone
Info
: ENaC
Provide the location, regulation and more information on
K+ channel
(collecting duct)
Location
: luminal
Regulation
: aldosterone
Info
: secretions allows a safety mechanism for when the individual experiences hyperkalemia
Provide the location, regulation and more information on
Na+/K+ ATPase
(collecting duct)
Location
: Basolateral
Regulation
: Aldosterone
Info
: maintains [ ] gradient
Define
hyperuricemia
a condition defined by an increase in uric acid (aka rate) in the blood
What causes gout and kidney stones?
hyperuricemia, more specifically, crystalization of uric acid in joints (
gout
) and kidney tubules/ureter/urther (
kidney stones
)
Define gout
swelling of the joints, especially the smaller ones, due to the deposition of crystalize uric acid
Define kidney stones
painful condition in which crystallized uric acid gets stuck in the tubules, ureter or urther
Common symptoms of kidney stones
pain and decreased urine output
Name 2 hormone systems that regulate Na+ levels
1)
Renin-Angiotensin-Aldosterone System
(RAAS) - sodium levels are low
2)
Atrial Natriuretic Peptide
(ANP) - sodium levels are high
Describe
Renin
an enzyme secreted into the blood stream by JG cells when there are low levels of sodium in the body, acts on the inactive angiotensin to convert it to
angiotensin I
(10 AA)
Describe Angiotensinogen
- constitutively produced by the liever
- 452 AAs long
- secreted into the blood stream
- not hormonally active
Describe Angiotensin I
- converted from angiotensinogen via renin
- 10 AAs
- not hormonally active
Describe ACE
- angiotensin convering enzyme
- produced by all endothelial cells
- highest in the pulmonary capillary bed
- converts angiotensin I into angiotensin II (8 AAs)
What makes Angiotensin II?
cleavage of angiotensinogen to angiotensin I and then to angiotensin II
Hormone properties of angiotensin II
peptide hormone, released into the blood stream when triggered
Stimulus for angiotensin II
renin release
General effect of Angiotensin II
causes an increase in sodium reabsorption in the proximal tubule
How does Angiotensin II affect Na+ reabsorption in the proximal tubule?
- ? activity of the Na+/H+ exchanger
- ? activity of the Na+/K+ ATPase
- Constrict both the afferent efferent arteriole, ?ing GFR and [Na+] filtered load
Why does slowing down fluid in the tubule increase Na+ reabsorption?
This allows more time for Na+ to be reabsorbed
Describe how angiotensin II carries out its action
Angiotensin II can be filtered and its receptors are on both the luminal and basolateral membranes. When Angiotensin II interacts with their receptors, the receptors produce local changes at their respective membranes
What is aldosterone made by?
the adrenal glands
What are the hormone properties of aldosterone?
steroid hormone
What is the stimulus of aldosterone?
- angiotensin II
- high potassium levels
- adrenal corticotropin hormone (ACTH)
General action of aldosterone
causes an increase in Na+ reabsorption in the collecting duct
How does Aldosterone increase Na+ reabsorption in the collecting duct?
- ? # of Na+ and K+ channels in the luminal membrane (translocation)
- ? activity of Na+/K+ ATPase (basolateral)
- ? expression level of both Na+ channels and Na+/K+ ATPases
How does binding of aldosterone affect Na+ reabsorption?
binding of aldosterone increases Na+ channels (reabsorption) and K+ channels (secretion) in the luminal membrane
Where are baroreceptors located?
- in the carotid sinus and special neural reflex directly to juxtaglomerular cells ? sympathetic
- at juxtaglomerular cells (aka intrarenal baroreceptors) ? afferent arteriole stretching
What stimulates JG cells to release renin?
- low intrarenal pressure of the afferent arterioles
- sympathetic innervation from carotid sinus (low BP)
- macular densa cells (Low Na+ in filtrate detected)
How do macula densa cells detect NaCl content?
macula densa cells detect NaCl content of the lumen through the activity of the Na-K-2Cl multiporter
Response of macula densa cells to high NaCl content in relation to GFR
- secrete ATP
- ATP is converted to adenosine extracellularly
- decrease local GFR
How does adenosine function in the kidneys?
acts as a vasoconstrictor that decreases local GFR
Response of macula densa cells to low NaCl content in relation to GFR
- release of Nitric Oxide (NO)
- increase in GFR
effect of NO in the kidneys
- NO is a vasodilator
- has a greater effect on the afferent arteriole and results in an ? in GFR
How do macula densa cells respond to high NaCl? (in relation to renin)
ATP and adenosine are released by macula densa cells and they bind to purinergic receptors on the JG cells. This causes a
decrease
in renin release
How do macula densa cells respond to low NaCl? (in relation to renin)
Low NaCl in the tubular filtrate cause macula densa cells to release
prostaglandins
which stimulate JG cells to
produce
and
release renin
How do macula densa cells respond to high tubular fluid flow?
- macula densa cells release ATP leading to the production of adenosine
- vasoconstriction
- decrease in GFR slowing down the fluid flow rate in the local tubule
How do macula densa cells respond to low tubular fluid flow?
- macula densa cells release NO as well as
prostaglandins
- ? GFR and ? fluid flow rate in the local nephron tubule
How do macula densa cells detect tubular flow?
Macula densa cells have
cilia
that bend less with decreased tubular flow and bend more with increased tubular flow
What is atrial natriuretic peptide made by?
cardiac atrial cells
What are the hormone properties of atrial natriuretic peptide?
peptide hormone, released into the blood when triggered
What is the stimulus of atrial natriuretic peptide?
high blood pressure
What are the sensors for atrial natriuretic peptide?
stretch receptors (located in
both
atrias)
General action of atrial natriuretic peptide
inhibit Na+ reabsorption
How does atrial natriuretic peptide inhibit Na+ reabsorption?
- ANP inhibits aldosterone secretion by the adrenal gland
- causes
dilation
of the
afferent arteriole
to ?GFR, ?ing flow throughout the tubule leading to ? Na+ excretion
What does high body levels of Na+ result in?
- a global release of ANP but also a release of adenosine
- effect of ANP outweighs the local effect of adenosine, especially in the nephron
What makes anti-diuretic hormone?
neuroendocrine cells in the hypothalamus
Where is anti-diuretic hormone stored?
posterior pituitary gland
What are the hormone properties of anti-diuretic hormone?
peptide hormone, released into the blood when triggered
What is the stimulus of anti-diuretic hormone?
- high plasma osmolarity
- low ECF volume (resulting in low BP)
- Angiotensin II
What are the sensors of anti-diuretic hormone
- osmoreceptors
- baroreceptors
Describe the relationship between osmoreceptors and ADH
increase in plasma osmolarity causes osmoreceptors to shrink in volume, triggering ADH release
Describe the relationship between baroreceptors and ADH
if ECF volume ?, causes the release of ADH by ?'d APs sent to the hypothalamus via the baroreceptors
Describe the action of ADH
?s the # of AQ II channels on the luminal membrane of the collecting duct (relocation of existing channels)
Where are ADH receptors located?
on the basolateral membrane
Describe how an increase in plasma osmolarity stimulates ADH release
An increase in osmolarity of ECF will cause the osmoreceptors near the 3rd ventricle to shrivel in response. The activity of neuroendocrine cells increases and an increase in ADH secretion into the blood increases. Water reabsorption increases and water e
Describe how a decrease in blood volume stimulates ADH release
A decrease in blood volume causes a decrease in MAP. Both will cause baroreceptors to respond by decreasing the amount of APs they fired. The activity of the neuroendocrine cells increases and more ADH is secreted. Water reabsorption increases and water e
What happens if both osmoreceptors and baroreceptors are stimulated?
A increase in plasma osmolarity and a decrease in plasma volume will cause a significant amount of ADH to be released into the blood stream. The converse is true, causing inhibition of ADH release.
What happens to ADH release when there is a decrease in both plasma osmolarity and blood volume under normal physiological conditions?
Under normal physiological conditions, the response to the osmoreceptors is deemed to be more improtant than the baroreceptors. Therefore, less ADH is released.
What happens to ADH release when there is a decrease in both plasma osmolarity and blood volume under severe conditions, such as hemorrhage?
The need to secrete ADH in response to the baroreceptors and volumereceptors (in atria) overcomes the need to inhibit ADH secretion in response to the osmolarities
What is the osmolarity of filtrate in the proximal tubule?
Approximately 300 mOsm because both ions and H2O are being reabsorbed
What happens to filtrate osmolarity in the descending limb of the loop of Henle?
Since only H2O is reabsorbed, filtrate osmolarity increases, a maximum concetration of ~1400 mOsm
What happens to filtrate osmolarity in the ascending limb of the loop of Henle?
Since only ions are reabsorbed, filtrate osmolarity decreases. An electrochemical gradient allows the ions to leak paracellularly.
What happens to filtrate osmolarity in the distal convoluted tubule?
The filtrate is most dilute here, ~100 mOsm.
What is the maximum difference between the filtrate and medulla?
200 mOsm
Describe urine osmolarity in the collecting duct
- If H2O can't be reabsorbed in the collecting duct, the urine will be very dilute (~100 mOsm) and at very large volumes.
- Maximal amount of ADH will lead to maximal H2O reabsorption, leading to urine with osmolarity of 1400 mOsm
Define Diuresis
An increase in urine production
Define natriuresis
an increase in Na+ excretion
Name examples of diuretics
1) Ethanol
2) AVP receptor antagonist
3) NKCC transporter antagonist
Describe Ethanol
(Diuretics)
- inhibits release of ADH
- causes ? in urine production
Describe AVP receptor antagonist)
(Diuretics)
- prevents ADH from binding and therefore preventing water reabsorption
- good for high BP and heart failure
Describe NKCC transporter antagonist
(Diuretics)
- ?s renal medulla osmolarity
- ? Na reabsorption, affecting medulla osmolarity
Describe
diabetes insipidus
- affects the ability of ADH to stimulate water reabsorption in the collecting duct of nephrons
- less water being reabsorbed leads to a much higher urine production, causing severe dehydration
What does it mean for diabetes insipidus to be neurogenic?
- failure to release ADH
- administer synthetic ADH to treat
What does it mean for diabetes insipidus to be nephrogenic
- failure of collecting duct cells to respond to ADH
- treat symptoms as necessary
Normal blood pH
~ 7.2 - 7.4
How do the kidneys help to maintain pH?
1) excrete excess H+ or HCO3-
2) Reabsorb most of the HCO3- in the proximal tubule
3) Create new bicarbonate ions by renal tubule cells
Name sources of acids in the body
1) Food
2) Metabolic intermediates
3) Lactic acid created by anaerobic metabolism
4) Production of CO2 by aerobic respiration
Food
(acid source)
acidic fruits, amino acids (ones that contain sulfur), fatty acids, etc.
Metabolic intermediates
(acid source)
lactate, pyruvate, citric acid cycle products
Production of CO2 by aerobic respiration
(acid source)
- CO2 combines with H2O to produce ccarbonic acid that dissociates int H+ and HCO3-
- biggest source of acid in the body
Name sources of bases in the body
1) Food
- some fruits and vegetables metabolize to HCO3-
Carbonic anhydrase
- enzyme that catalyzes the forward and reverse reaction of bicarbonate synthesis
- depending on the cell, it can be found in either the luminal membrane, basolateral membrane or cytosol
What must happen before HCO3- is reabsorbed?
It must first be converted to CO2. This is accomplished by letting H+ interact with the HCO3- to convert it to CO2 and H2O. Once the CO2 has diffused into the cells, it will react with H2O and be catalyzed by carbonic anhydrase back into HCO3- and H+
How does HCO3- get reabsorbed into the capillaries?
It is transported across the basolateral membrane of the tubule cells via a Na+/HCO3- symporter. The gradient of the HCO3- is driving the transport, NOT the Na+ gradient
What collecting duct cells secrete H+ ions into the lumen?
Type A intercalated cells
Describe the transporters of Type A intercalated cells of the collecting duct.
Luminal membrane transporters
- H+ ATPase
- H+/K+ ATPase
- translocated to the membrane
- require energy
Basolateral membrane transporters
- HCO3-/Cl- antiporter
- permanently embedded in the membrane
- driven by Cl- [ ] gradient
What activates Type A intercalated cells of the collecting duct?
the binding of H+ to receptors on the cells' basolateral membrane
What are some conditions associated with an increase in blood [H+]?
- acidosis
- hyperkalemia (high blood [K+])
What are the collecting duct cells that secrete HCO3- into the lumen?
Type B intercalated cells
Describe the transporters in the type B intercalated cells of the collecting duct
Luminal membrane transporters
- HCO3-/Cl- antiporter
- translocated into the membrane
- driven by Cl- [ ] gradient
Basolateral membrane transporters
- H+ ATPase
- H+/K+ ATPase antiport
- require energy
What are conditions commonly associated with increased blood pH?
- alkalosis
- hypokalemia
Name 4 causes of acid/base disturbances
1) Metabolic Acidosis
2) Respiratory Acidosis
3) Metabolic Alkalosis
4) Respiratory Alkalosis
Describe metabolic acidosis
- due to excessive breakdown of fats or certain amino acids
- can be caused by excessive ingestion of aspirin
- can be caused by ingestion of methanol and antifreeze
- increases H+ load
Causes of respiratory acidosis
- hypoventilation
- respiratory depression due to drugs (including alcohol)
- airway resistance due to asthma
- diseases that affect gas exchange in the lungs (e.g. fibrosis and muscle weakness from muscular dystrophy)
Causes of Metabolic Alkalosis
- excessive loss of H+ due to excessive vomiting
- excessive ingestion of bicarbonate-containing antacids
Causes of respiratory alkalosis
results from too much CO2 being expelled through the lungs via hyperventilation