Renal Physiology

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