Urinary Flashcards
Path of blood flow though kidney
1)renal artery
2)segmental arteries
3)interlobular arteries
4)arcuate arteries
5)cortical radiate arteries
6)A. Arterioles
7)glomeruli
8)E. Arterioles
9)peritubular capillaries
10) vasa recta
11) cortical radiate veins
12) arcuate veins
13) interlobular veins
14)renal vein
Interlobular arteries location
Between renal pyramids
Arcuate arteries location
At border of renal cortex or medulla
Cortical radiate arteries location
Extend into renal cortex
Vasa recta location
-in juxta. Nephrons
-supply medullar
Glomerulus
1) endothelial lining (fenestrated)
2) glomerular basement membrane
-extremely (-) charged due to heparin sulfate on lamina rara interna and external
Lamina rara interna
-Fenestrated ~10% surface area (50-100nm pores in capillaries)
-Freely permeable to everything • except cells and platelets
-“Endothelial layer”
• Part of membrane closest to endothelial cells
-Made up of specific types of molecules
• E.g., proteoglycans
-Has heparin sulfate
Lamina densa
made of Type IV collagen and laminins
Lamina rara externa
-Also has heparin sulfate
-Surround or cling to glomerular capillaries
-Rest on basement membrane and face Bowman’s
space
-have an unusual octopus-like structure
Visceral layer of bowman’s capsule
-Surround or cling to glomerular capillaries
-rest on the basement membrane and face Bowman’s
space
-Podocytes
-have an unusual octopus-like structure
-foot processes / “small fingers”
-Filtration slit
-extremely thin processes (25-30nm)
-spaces in between podocytes
-Slit diaphragms
-bridge slits between podocytes
-crucial for filtration barrier selectivity
-prevent excess leak of plasma protein (albumin)
-made of Nephrin
Filtration: substances that can pass through
1)Electrolytes
-E.g., HCO3–, Na+, K+, Cl–, Ca2+, Mg2+, H2O
-Despite the negative charge on some of these
electrolytes, they’re very small; Hence, they will
get freely filtered
2)Non-negatively charged low-Molecular weight molecules
-E.g., glucose, amino acids, lipids, urea, creatinine, vitamins
Filtration substances will move through…
fenestration pores ➡️glomerular basement membrane ➡️ filtration slit ➡️nephrin ➡️Proximal Convoluted Tubule
Glomerular mesengial cells location
Center of glomerulus between and w/in capillary loops
Mesengial cells function
-phagocytose and rem. Trapped macromolecules from basement membrane capillaries (such as slit diaphragm)
-contain myofilaments (contracts in response to a variety of stimuli)
-ex. Vascular smooth muscle cells
-control amount of blood flow coming in through A. Arteriole and in through glomerular capillaries
Juxtaglomerular cells
-Connected to mesengial cells by gap junctions (mesengial cells all for (+) ions to ➕JGC to release renin)
-baroreceptors
-produce renin
-importance in maintenance of BP
Glomerular filtration rate (GFR)
Plasma volume being filtered out of the glomerulus into the bowman’s capsule every minute
-On average, 125 mL/min
- Per min., 1.2L goes to AA ➡️ 625mL used in filtration process ➡️ only 20% (125mL) is filtered
Glomerular filtration rate equation
Glomerular filtration rate = net filtration pressure x filtratrion coefficient
GFR = NFP x KF
⬆️NFP➡️⬆️GFR
⬆️KF➡️⬆️GFR
Net filtration Pressures
1) glomerular hydrostatic pressure (GHP)
2) colloid osmotic pressure (COP)
3) capsular hydrostatic pressure (CHP)
4) capsular osmotic pressure
Glomerular Hydrostatic Pressure (GHP)
Force that pushes plasma out of the glomerular capsule into the bowman’s space
-Directly dependent on systolic blood pressure
• ⬆️BP = ⬆️GHP
• ⬇️BP = ⬇️GHP
-Average value: 55 mmHg
Colloid Osmotic Pressure (COP)
-Exerted by plasma proteins like albumin -Keeps water in the blood
-Average value: 30 mmHg
-Clinical Correlates:
• Multiple myeloma
o ⬆️Amount of proteins in blood ➡️holds onto more water in the blood ➡️ ⬆️COP
• Hypoproteinemia
o Loses substances/proteins ➡️can’t hold on to water as much ➡️ ⬇️COP
Capsular Hydrostatic Pressure (CHP)
-As fluid is being filtered out, the pressure will push things back into the capillary bed
-By the pressure build-up in the Bowman’s capsule
-Average value: 15 mmHg
-Clinical Correlate:
• Renal calculi
o Kidney stone stuck in nephron
o > 5mm in diameter
o Pressure backs up and starts increasing ➡️ ⬆️CHP
• Hydronephrosis
o Due to renal ptosis
o Rapid weight loss
o ⬆️CHP ➡️more fluid being pushed back into the glomeruli and not much glomerular filtration
Capsular Osmotic Pressure
-As long as the filtration membrane is intact, there should be no proteins in the Bowman’s capsule
-Average value: 0 mmHg
NFP equation
NFP = GHP - (COP + CHP)
10mmHg = 55mmHg - (30mmHg +15 mmHg)
Filtration Coefficients
1) surface area (SA)
2) permeability of glomerulus
Filtration coefficient: Surface area (SA)
-Lower surface area ➡️lower GFR ➡️ -Larger SA ➡️greater GFR
-Clinical Correlate
• Certain conditions can change or affect the SA
• Diabetic Nephropathy
o Proteins and deposits that make the glomeruli thicker, lessening the SA, and lowering the GFR
Filtration coefficient: permeability of glomerulus
-Lesser channels, lower GFR
-More channels, higher GFR
-Clinical Correlate: Glomerulonephritis
• Makes basement membrane very porous ➡️higher GFR ➡️lose more proteins
Osmolality
Volume of particles per kg of solvent (mol/kg)
-in glomerulus: blood is 300mosm/L (comes into PCT at 300mosm/L)
-mosm= milliosmoles
(Note: osmolarity= mol/L
Kg=L)
Tubular secretion of PCT
-Blood➡️ kidney tubule
-active process: requires ATP
Tubular reabsorption of PCT
-kidney tubule➡️ blood
-depending on chemicals being reabsorbed, it could be active or passive
Na+/K+ ATPase: PCT
Pumps 3 Na+ out of cell and 2K+ into cell
-move against their concentration gradients from areas of ⬇️ to ⬆️ concentration
-location: basolateral
-primary active transport: requires ATP
-97% of K+ is inside the cell
-⬇️[Na+] and ⬆️[K+] -inside cell
Secondary active transport: PCT
-Passive diffusion of one substance helps facilitate the active transport of another substance
-Can transport two things at once inside the cell
Examples of secondary active transport: PCT
1)Na+/ glucose contransporter
2) Na+/ AA contransporter
3) Na+/ lactate contransporter
Na+/ glucose cotransporter: PCT
-secondary active transport
-location: applical membrane
-Na+: ⬇️Na+ inside cell➡️ moving passively along its concentration gradient
-Glucose:
-⬆️Glucose inside cell
Na+ helps move Glucose against its concentration gradient
-when inside cell: there are specific transporters on basolateral membrane that transport Glucose out of cell and into bloodstream (tubular reabsorption)
-same mechanism w/ Na+/AA cotransporter and Na+/lactate cotransporter
-100% glucose, AA, and lactate reabsorbed
How does HCO3- go into the cell? (PCT)
CO2 + H2O ➡️ H2CO3 ➡️ H+ + HCO3–
-This reaction is catalyzed by the enzyme carbonic anhydrase
-Carbon Dioxide (CO2)
-Can be found in our blood
-Can move into the cell (through basolateral membrane) and react with water to form sodium bicarbonate
-Sodium Bicarbonate (H2CO3)
-Unstable; dissociates into a proton (H+) and bicarbonate (HCO3–)
What happens to H+ after converted from H2CO3? (PCT)
-Sodium-Hydrogen Antiporter
• Secondary Active Transport
• As Na+ moves through the channel to go in the
cell, it helps push H+ out
-H+ combines with HCO3– outside of the cell
• Resulting H2CO3 is converted by carbonic anhydrase into CO2 and H2O
What happens to HCO3- after being converted from H2CO3? (PCT)
90% HCO3- gets pushed into blood
Osmosis: reabsorption (PCT)
-obligatory water reabsorption- H2O feels obliged to follow Na+
-H2O moves by osmosis
-kidney tubules➡️ blood (reabsorption)
-65% of Na+ reabsorbed➡️ 65% of water reabsorbed
Paracellular transport (PCT)
-How ions move in between the cell to the blood
-Ca2+, Mg2+, K+, Cl–
-Very little calcium and magnesium are reabsorbed in this area
-About 50% of Cl– is reabsorbed via this -mechanism About 55% of K+ is reabsorbed via this mechanism
Na+/Cl- symporter (PCT)
Moves Na+ and Cl- into cell
-aplical membrane
- they are then pushed into the blood (reabsorption)
Lipids (PCT)
-lipid-soluble substances can pass through the phospholipid bilayer
-E.g., Urea
-Not all of it gets reabsorbed
-Can pass through the membrane and into the blood
Small proteins (PTC)
Insulin and Hb
-There are specific protein receptors on the membrane
-If these small proteins are filtered, they can get
caught on these receptors
-proteins are endocytosed and taken into the cell
-These are combined inside the cell with lysozymes
• Hydrolytic enzymes
• Break down the proteins into their constituent amino acids
-Receptors are recycled
-The vesicle fuses with the cell membrane and
amino acids are released into the blood
Na+/phosphate symporter (PTC)
Channel normally brings both Na+ and HPO42– in
-There’s a receptor for the PTH on the cell of the proximal convoluted tubule
-PTH: Para-Thyroid Hormone
• Binds with the receptor and activates the G- stimulatory protein
• G-stimulatory protein activates adenylate cyclase
• Adenylate cyclase converts ATP ➡️cAMP
o cAMP ➡️Protein Kinase A
-Protein Kinase A
• Puts phosphates on the transporter
-Transporter is inhibited
• Phosphates don’t get reabsorbed; they get excreted
Metabolic acidosis
-Glutamine
oSpecific type of amino acid
o Can undergo deamination(remove amine group and acidify)
-Has two amine groups
• After the two amine groups are removed, glutamine is acidified too
-Results into 2 ammonium ions
-Oxidized into 2 bicarbonate ions
• Remove electrons/hydrogen
-Normal blood pH is 7.35-7.45
-In metabolic acidosis
o Blood pH is low ( < 7.35)
o Body has to compensate for that
-Bicarbonate from the glutamine will be taken into the blood
• Bring the pH back up
-Chloride ion will need to go out of the blood into
the cell
-The ammonium ions will be pushed out of the cell and into the kidney
• Will dissociate into ammonia (NH3) and H+
Recap: CO2 + H2O H2CO3 H+ + HCO3–
o When bicarbonate goes out of the cell and into the
bloodstream, it makes the pH go up.
Tubular secretion (PCT)
In the blood, there are certain things we can’t get rid of.
-Because it got reabsorbed, or we can’t filter it
-E.g., certain drugs (penicillin, cephalous porins, methotrexate)
-Similar with uric acid, bile salts, morphine, organic acids
-The process of getting these excreted into the kidney tubules is an active process
-Requires ATP
Nephron is a made up of…
1)Renal corpuscle
- Glomerulus
-Bowman’s Capsule
-Process: Glomerular Filtration
2)Proximal Convoluted Tubule
-Processes
• Tubular Secretion
• Tubular Reabsorption
3)Loop of Henle
4)Distal Convoluted Tubule
Hypertonic
⬆️osmolality
⬆️solutes (in blood)
⬇️H2O (in blood)
Hypotonic
⬇️osmolality
⬇️solutes (in blood)
⬆️H2O (in blood)
Isotonic
Solutes= H2O
Osmolality values
-inside the glomerulus: ~300 mosm
o blood plasma
-In Bowman’s capsule: ~300 mosm
o Isotonic with the blood plasma
-When it leaves the PCT: 300 mosm
o Still isotonic with the blood plasma
o It didn’t change because equal amounts of solutes and water were being reabsorbed
-Due to obligatory water reabsorption
o Isotonic with the blood plasma
-Medullary interstitial osmolality gets saltier or more hypertonic as we go down the renal medulla
Why does medullary interstitial osmolality get saltier?
Na+/K+/2Cl– Cotransporter
o Transports sodium, chloride, and potassium from lumen of filtrate into tubule cell of ascending limb
o There are specific channels for each ion in the cell
-Na+ and Cl– will be pushed out
• Increases osmolality (saltier)
-Only some of the K+ leaks out, some of the K+ stays out
• Some K+ gets pushed back in the lumen
o Creates depolarization of the inner side of the membrane of the ascending limb
-Causes Mg2+ and Ca2+ to undergo paracellular transport
Descending limb: impermeable to solute
Counter-current multiplier mechanism
-water will flow out to the area where the salt is
-from D. Limb➡️ A. Limb
-due to obligatory water reabsorption
-via aquaporins
-medullary interstitial space: space as we go down ➡️ more water will leave as we go down D. Limb
-1200mosm at turn: hypertonic
-goes up A. Limb: ⬇️osmolality b/c A. limb is losing salt
-120-200mosm when it hits DCT (hypotonic)
Vasa recta
-Peritubular capillary in the medulla
-Branch of the Efferent Arteriole
-Known as the “Counter-Current Exchanger”
Blood flow to vasa recta is really slow
Vasa Recta functions
1)Prevents rapid removal of sodium chloride
-Does not develop the medullary interstitial gradient
or the counter-current multiplier mechanism
-It’s maintaining the gradient; not generating it
2)Carries Oxygen
-Cells depend on oxygen
-Vasa recta also delivers oxygen and nutrients
Loop of henle function
Reabsorption
D. Limb
-H2O permeable
-solute impermeable
-aquaporin-1
A. Limb
-H20 impermeable
-solute permeable
-Na+/K+/Cl- cotransporter
-pushes these solutes out into medullary interstitum (salty, high osmolality)
-some K+ gets pushed back in the lumen, creating a depolarization on inner side of membrane of A. Limb
-causes Mg2+ and Ca2+ to undergo paracellular transport
Salty medullary interstium➡️ water is pulled out. Importance:
o In the PCT
-65% of water was reabsorbed
-65% of sodium was reabsorbed
-300 mosm
o In the descending limb,
-15% of water was absorbed
o Going into Distal Convoluted Tubule (DCT),
-There’s only ~20% water left
-There’s only ~10% sodium left (25% of
sodium was reabsorbed in the thick
ascending limb of the loop of Henle)
-100-200 mosm
Na+/K+ pump (early DCT)
-specialized channel in basolateral
-requires ATP
-pumps 3Na+ out and 2 K+ in
Diuresis
Release more urine than normal
Na+/Cl- symporter (early DCT)
-specialized transporters, aplical
-Na+: going out of cell via Na+/K+ pump: DCT has ⬆️[Na+]
-going along its concentration gradient
-only 5-6% of Na+ is being reabsorbed
-4-5% left
-Cl- has a special channel that pumps it into blood
-➖ by thiazide
Thiazide relationship with Na+/Cl- symporter
-diruetic
-➖Na+/Cl- symporter
-affect salt and water reabsorption
-instead of reabsorbing 5-6% back, you’ll lose them in urine
-lose a bit of BV (Diuresis)
⬇️Ca2+ in the blood (early DCT)
-➕PTH release
-PTH has receptor on DCT
-➕2nd messenger system: protein kinase A
-protein kinase A ➕ Ca2+ modulated channels
-channels pull Ca2+ into cell
-channels sensitive to PTH levels
-even if ⬇️Ca2+ in blood, there’s still less Ca2+ inside cell
-Ca2+ will move against its concentration gradient
Late DCT
-generally impermeable to water
-has specialized cells responsible for responding to aldosterone
Aldosterone
Steroid hormone produced in top part of (globular cells) of adrenal gland
-able to pass through lipid bi layer b/c it is a steroid hormone
Aldosterone stimulus for release
1)angiotensin-2: wants to ⬆️BP
2)hyponatremia: ⬇️[Na+] in blood
3)hyperkalemia: ⬆️[K+] in blood
Effects of aldosterone (late DCT)
1)Na+/K+ transporter
-basolateral
-active transport
-3Na+ out 2K+ in
-Na+ leaves ➡️⬇️[Na+] inside cell
-K+ enters ➡️⬆️[K+]
2)Na+ channels
-aplical
-Na+ is allowed to go inside due to effects of Na+/K+ transporter
3)K+ channels
-aplical
-⬆️[K+] in cell, channel will move it out of cell where it will eventually be excreted into urine
ADH (late DCT)
-presence of ADH will open aquaporins
-water will have to follow salt into cell
-⬆️H2O volume getting pulled into blood➡️⬆️BP
Intercalated cells reabsorb _ and secrete _
K+ and HCO3-; hydrogen
Aldosterone causes _ reabsorption and _ secretion
Na+; K+
Intercalated cells location
Late DCT and CD
Intercalated A-cell
Responds to acidosis
-respiratory acidosis
-metabolic acidosis
scenario of how intercalated A- cells work
⬆️CO2 in the blood
-acidosis: ⬇️pH = ⬆️H+
o CO2
-Found in our blood; moves into the cell, and combines with water to form H2CO3
-Catalyzed by enzyme carbonic anhydrase
o Sodium Bicarbonate (H2CO3): Unstable; dissociates into proton and HCO3
o Protons (H+)
-H-K-ATPase
-Both ions are moving against their concentration gradients
• K+ goes into the cell
• H+ goes out of the cell
-Body needs to secrete substances it doesn’t like
• Ammonia (NH3): Can be excreted out into the urine where it combines with the protons to produce ammonium (NH4 +)
o Bicarbonate (HCO3–): Can be pumped out of the cell into the blood via the HCO3–/Cl– transporter
-➡️⬆️pH b/c HCO3- will eventually tie up H+
Intercalated B-cells
Respond to alkalosis
-respiratory alkalosis
-metabolic alkalosis
Scenario on how intercalated B-cells work
-The same pathway as intercalated-A cell, but flipped.
o Get rid of bicarbonate instead of the proton
o Reabsorb proton into the blood instead of bicarbonate
-⬆️pH, ⬇️H+, ⬆️HCO3
o Carbon Dioxide (CO2)
-Found in our blood; moves into the cell, and combines with water to form H2CO3
-Catalyzed by enzyme carbonic anhydrase
o Sodium Bicarbonate (H2CO3)
- Unstable; dissociates into proton and HCO3
o Bicarbonate (HCO3 –)
-HCO3–/Cl– transporter
• HCO3– goes out of the cell
o pumped out of the cell into the urine
• Cl– goes into the cell
o Cl– will exit the cell via the chloride channels on the basolateral membrane
o Protons (H+)
-H-K-ATPase
• ATP-dependent pathway
o Both ions are moving against their concentration gradients
• K+ goes into the cell
• H+ goes out of the cell into the blood
-➡️⬇️pH
Principal cells
-Cells that maintain mineral and water balance
-Hypothalamus
o Collection of neurons from the supraoptic nucleus
o Axons move through from the hypothalamus to the posterior pituitary
o When stimulated, it will release ADH
Secretions of collecting duct
-H+
-creatinine
-HCO3-
-drugs
-toxins
-NH3
ADH works in
Late DCT and CD
ADH stimulus
1) High plasma osmolality
o ADH wants to have more water in the blood, which means that the plasma osmolality was initially high
2) Angiotensin-II
o To increase blood pressure
ADH process
-ADH binds to the vasopressin receptor (on the principal cell) in the collecting duct of the kidneys,
o Will activate the secondary messenger system
-cAMP activates Protein Kinase A
-phosphorylates proteins on vescicles
-pre-synthesized vescicles with proteins and channels (aquaporins)
-Activates aquaporin-II
-Fuses with the cell membrane
-There’s aquaporin-III and aquaporin-IV in the basolateral membrane
-Water goes out aquaporin-II, then passes through aquaporins III & IV ➡️ goes into the blood➡️⬆️ blood volume➡️⬆️blood pressure
o Also reaches normal plasma osmolality ➡️isotonic
Ca2+ reabsorption
Dependent on presence of PTH
H2O reabsorption
-65% reabsorbed in PCT
-15% reabsorbed in D. Limb of loop of henle
-20% reabsorbed in DCT
-dependent on aquaporin-2, which is dependent on ADH
-⬆️ADH➡️⬆️H2O reabsorption
-⬇️ADH➡️⬇️H2O reabsorption
Na+ reabsorption
-65% reabsorbed in PCT
-25% reabsorbed in A. Limb of loop of henle
-5-6% reabsorbed in early DCT
-remaining 4-5% is reabsorbed depending on presence of aldosterone
Juxtaglomerular apparatus
Region of nephron where DCT and A Arteriole come in contact to regulate filtration rate
Basolateral membrane
Cell membrane oriented away from lumen of nephron
Apical membrane
Cell membrane oriented towards lumen of nephron
Podocytes
-wrap around arterioles of glomerulus
-cells of bowman’s capsule
-type of epithelial cell
Vasa recta
Peritubular capillary network present within the deep part of the medulla
-Known as the “Counter-Current Exchanger”
-As the ascending limb goes up, it pumps the solutes out ➡️pulling water out of the descending limb
o Solutes: Mg2+, Ca2+, K+, Cl–, Na+
-Vasa Recta gets saltier as we go down
o due to the Counter-Current Multiplier Mechanism
o Water wants to flow out towards where it’s salty
o NaCl is pulled into the Vasa Recta
-Processes reverses when vasa recta turns and goes up
o Water now wants to go back inside
o NaCl is being pushed back inside as we go up
Vasa recta functions
1)Prevents rapid removal of sodium chloride
-When blood enters, it’s 300 mosm
-When blood leaves, it’s 325 mosm
• This implies that the vasa recta kept a bit of
-NaCl with it to prevent rapid removal
2) Carries Oxygen
-Cells depend on oxygen
-Vasa recta also delivers oxygen and nutrients
Urea recycling
A lot of urea gets lost in the urine, but some are recycled
-Urea gets reabsorbed in the last part of the collecting duct
o after all the water has been reabsorbed, [urea] starts increasing
-It then moves out of the collecting duct and into the medullary interstitium via facilitated diffusion
o It gets reabsorbed in the ascending limb of Loop of Henle
o At the same time, urea accumulates outside
Purpose of urea
1) makes concentrated urine
2) contributes to medullary gradient- helps to make medulla more salty
Autoregulation
Ability of the kidney to modify BF and urine output
How?
1) intrinsic mechanism
-myogenic mechanism
-tubuloglomerular feedback
2) extrinsic mechanism
-SNS
-RAAS
Myogenic mechanism
Intrinsic
-Myogenic = muscle of afferent arteriole
-Blood pressure is a surrogate of the glomerular hydrostatic pressure
o Glomerular hydrostatic pressure (GHP): pressure inside the capillaries exerted to push substances out of the capillaries and into the Bowman’s capsule
Myogenic mechanism: ⬆️BP
⬆️BP → ⬆️GHP → ⬆️GFR
-counter acted by vasoconstriction of AA
-Higher glomerular filtration rate (GFR)= more urine
-Kidneys modulate the GFR so that it is not too excessive making too much urine, or the blood pressure does not
remain too high causing injury on the glomerular capillaries
(i) Mechanism:
-Blood flows through the AA then to the EA
-↑BP = more blood to the AA
o Na channels in the smooth muscle is sensitive to stretch: inside of of smooth muscle becomes very (+)➡️ Ca2+ is unloaded into smooth muscle cell➡️vascocontracts
-AA vasoconstricts → ↓glomerular blood flow (GBF) →↓filtered plasma and other substance (↓GFR)
Myogenic mechanism: ⬇️BP
↓BP → ↓GHP → ↓GFR
-↓BP = ↓urine = can cause kidney injury
-How does the kidney prevent it?
(i) Mechanism:
-↓BP = ↓blood to the AA = ↓stretch on the AA
-↓stretch → ↓Na+ enter in the smooth muscle cell → less positive charge → ↓Ca2+ released by the sarcoplasmic
reticulum → ↓contraction = relaxation
-vasodilation
Macula densa cells location
DCT
Macula densa cells location
DCT
Tubuloglomerular feedback
-intrinsic
-this mechanism is sensitive to NaCl
-NaCl gets reabsorbed in PCT
Tubuloglomerular feedback: ⬆️BP
↑BP = ↑GFR = ↑NaCl excretion into the kidney tubules
-When NaCl transporters in the PCT are saturated, NaCl can escape and move to the LH and then to the DCT where macula densa cells are found
o Special NaCl sensors
o Release adenosine when it detects ↑NaCl
-Adenosine functions to:
(1 vasoconstrict AA → ↓GBF → ↓GFR → ↓NaCl being filtered
(2 inhibit juxtaglomerular (JG) cells → ↓renin →↓blood pressure
Tubuloglomerular feedback: ⬇️BP
↓BP = ↓GFR = ↓NaCl excretion into the kidney tubules
-When macula densa cells detect ↓NaCl in DCT, they release PGI2 and nitric oxide (NO)
-PGI2 and NO function to:
(1) vasodilate the AA → ↑GBF → ↑GFR → ↑NaCl filtered
Extrinsic mechanisms
Kicks in when BP is relatively low
SNS stimulus
Stimulus: ↓↓↓SBP → MAP < 65 mmHg
o MAP (mean arterial pressure): measure of perfusion
o When MAP < 65 mmHg, kidney is not perfused; blood flow is redirected to other “more important” organs
such as the heart, brain and muscles
Effects of SNS
-↓BP triggers baroreceptors → CN IX and CN X send ↓signals to the medulla
-Medulla activates sympathetic nerve fibers in the thoracic
part causing release of NE and epinephrine
Effects of SNS: the ♥️
-NE and epinephrine act on the nodal system → ↑HR, ↑SV
(due to ↑contractility) → ↑CO → ↑BP
o To increase blood flow in the kidneys to avoid injury
-NE and epi stimulate the β1 receptors in the nodal
system and contractile fibers → ↑HR and ↑SV, respectively
o Chronotropic: change in heart rate
o Ionotropic: change in contractility
Effects of SNS AA and AE
SNS release NE and EPI that act on the α1 receptors of the AA and EA → vasoconstriction → ↓GBF → ↓GFR
Effects of SNS: systemic vessels
NE and EPI act on the α1 receptors on the systemic vessels → vasoconstriction of multiple vessels →↑systemic vascular resistance (SVR) → ↑BP
Effects of SNS juxtaglomerular cells
NE and EPI stimulate the β1 receptors on the JG cells → ↑renin → activates angiotensin II →→→ ↑BP
Effects of SNS summary
1) Increase HR and SV
2) Vasoconstriction of the afferent and efferent arterioles
3) Vasoconstriction of the systemic vessels → ↑SVR
4) Triggers release of renin
RAAS
↓BP → ↓GFR
-Juxtoglomerular cells are sensitive to changes in blood pressure
o When BP is low, JG cells release renin
-Renin cleaves angiotensinogen to produce angiotensin I
-Angiotensin I move to the capillaries in the lungs and get converted to angiotensin II by angiotensin converting enzyme (ACE)
Functions of angiotensin 2
1) ADH release
-angiotensin 2 ➕ hypothalamus that triggers release of ADH from pituitary
-ADH
-acts on aquaporin on CD to reabsorb water
-⬆️H2O in blood➡️⬆️BV➡️⬆️BP
2) thirst
-makes you thirsty➡️ ⬆️water intake➡️⬆️BV➡️BP
3) aldosterone release
-angiotensin 2 ➕ release of aldosterone from adrenal gland
-function: act on DCT to make them permeable to water and Na+
⬆️Na+ and ⬆️H2O ➡️⬆️BV and ⬆️BP
4) vasoconstriction of EA and ⬆️GFR
-angiotensin 2 binds on the receptor on the EA➡️ vasoconstriction
-less blood can escape from glomerulus, more blood stays in glomerulus➡️ more blood filtered out➡️⬆️GFR
-angiotensin 2 acts on PCT to cause ⬆️reabsorption of Na+ and H2O
-⬆️Na+ and ⬆️H2O➡️⬆️BV➡️⬆️BP
5) vasoconstriction of systemic blood vessels
-angiotensin 2 acts on systemic blood vessels➡️ potent vasoconstriction
➡️⬆️SV➡️⬆️BP➡️⬆️GFR
ANP
Released from the heart in cases of ↑BP
Function: can block any function of the angiotensin II
1)Blocks ADH release = no water and Na+ reabsorption = urinate water and Na+ = ↓blood volume
2) Blocks aldosterone release = no water and Na+reabsorption = urinate water and Na+ = ↓blood volume
3) prevents vasoconstriction= ⬇️GFR
4) vasodilation of blood vessels =⬇️SVR➡️⬇️BP
Thiazide
Promotes Na+/Cl- loss in DCT
Loop duiretic
Interfere with Na+/Cl- pumps in loop of henle
Olguria
Low urine volume 50-500ml a day
Anuria
Little to no volume of urine 0-50ml/day
Polyuria
High urine volume- well over 2000ml a day
Cystitis
UTI- inflammation of the bladder
Chronic renal disease
GFR <60ml/min for 3 mo
-Diabetes mellitus
-hypertension
Renal failure
GFR < 15ml/min
Causes uremia – ionic and hormonal imbalances; metabolic abnormalities; toxic molecule accumulation
Pyelitits
Bacterial infection that causes inflammation of renal pelvis or mucous membrane of kidney’s pelvis
