Renal Flashcards
What are the determinants of Glomerular filtration?
Effective filtration pressure = ~20 torr
What are the determinants of renal blood flow?
How is capillary pressure maintained despite fluctuating arterial BP?
- RBF maintaining by matching of pressure and renal vascular resistance
-
Autoregulation occurs via two mechanisms
- The vascular response: myogenic (bayliss reflex); contracting of SMC in response to stretch
-
Glomerular-vascular:
- change in [NaCl] @ thick ascending limb
- ↑ [NaCl] -> afferent constriction
What percentage of Na+ is reabsorbed at each of the 4 key areas in the nephron?
- PCT – 67%
- TAL – 25%
- DCT – 5%
- CD – 3%
-> 0.4% filtered load remaining
How is sodium handled at the PCT, TAL, DCT and CD? (images)
- PCT
- TAL
- DCT
- CD
What are the two types of glucose transporters in the apical membrane of the PCT?
- SGLT2- not very saturable, low affinity
- SGLT1- (late PCT) – low saturability, very high affinity (mops up remaining glucose)
What are the primary mechanisms that regulate [K+] in the ECF?
PCT
TAL
CD.
- Intercalated cells in late distal tubules and CD
- Principal cells in late distal tubules and CD - aldosterone mediated
Explain the counter current multiplier in respect the development of a hyperosmotic medullary insterstitium.
Descending limb: only permeable to water
Ascending limb: only permeable to Na+ (diluting segment)
- Active pump in TAL pumps Na+ into interstitium, establishing a 200 mOsm/L gradient between tubular fluid and interstitial fluid.
- The TDL then equalibriates (400mosm/L) with the increase interstitial osmolarity, as water leaves into the interstitium (interstitium osmolarity maintain dt. constant active transport of Na+ from TAL).
- New fluid is then pushed through from TDL, causing hyperosmolar fluid from TDL to flow into the TAL, this fluid then again establishes the 200mOsm/L gradient, but now at the higher osmolarity of 500mOsm/L
- -> this repetition is the counter current multiplier – allows a very high osmolarity to be established despite only a 200mOsm/L gradient being capable of being established between lumen and interstitium at the loop of henle
- A very dilute tubular fluid is delivered to DCT and CD -> allows for modulation of fluid balance.
- Vasa recta also run in similar counter current pathway -> prevents washing out of establishing medullary gradient.
-
Urea also contributes about 50% of medullary osmolarity,
- very high delivery of urea to medullary CD
- -> urea diffuses into interstitium -> horizontal transfer to Loop of Henle where it is secreted into luminal fluid, and urea recirculates each time contributing to higher osmolarity of interstitium.
- Therefore, low protein diets -> less ability to concentrate urine.
How does ADH promote H20 reabsoprtion?
- Increase in ADH = Increase in number of aquaporins open.
- Aquaporins are the channels that H20 use for osmosis
How does ADH promote urea recycling?
Increase levels of ADH in CD, promotes UT-A1 transporters to open so urea can be reabsorbed into the interstitial fluid.
How does the counter current exchanger maintain gradient
- Vasa recta is freely permeable to NaCl and H20.
- Therefore passive diffusion out of solute and passive diffusion in out H20 is easily performed.
- This ensures the blood and the surrounding fluid are in equilibrium.
How does the countercurrent multiplier achieve its role
- (1) In TAL: Active transport pumps NaCl out into interstitial fluid. Creating a concentration gradient of 200mosm between the tubule and interstitial fluid.
- (2) The TDL equilibrates with the new increase osmolality of the interstitial fluid by pumping H20 out via passive diffusion.
- (3) New fluid arrives in TDL, this moves the hyperosmolality fluid up into in the TAL, which then again promotes the active pumping of Nacl out. This fluid again establishes a 200mosm gradient but just at a higher osmolarity of 500mosmol/L.
How is ADH stimulated
Plasma osmolality >300mosm
Osmolality
The number of dissolved solutes in 1kg of fluid
Role of ADH
Promotes the reabsorption of H20. Thus contributes to urine being more concentrated.
Structures responsible for diluting or concentrating urine
- Vasa Recta
- Loop of Henle
- Collecting Duct
Two mechanisms of countercurrent
- Countercurrent Multiplier: Loop of Henle
- Countercurrent exchanger: Vasa Recta
What is important to remember about Counter current exchanger
Vasa recta does not contribute to gradient but rather it protects it.
What is the role of the countercurrent exchanger
The vasa recta ensures the concentration gradient is maintained so the counter current multiplier can continue to dilute/concentrate urine
What is the role of the countercurrent mechanism
Keep solute of body fluid ~300mosm by regulating urine concentration and volume
What is the role of the countercurrent mulitpier
Main goal is to concentrate urine
What is the role of urea
Urea enhances urine to be concentrated.
What are the different classes of diuretics
REMEMBER: Over Caffeinated Ladies Talk Intensely After Midnight
- Osmotic diuretic
- Carbonic anhydrase
- Loop diuretics
- Thiazides
- Inhibitors of ENaCs
- Aldosterone antagonist
- Methlyxandithine
Give an example of Osmotic diuretic and where it acts long the nephron
- E.g. Mannitol
- PT and TAL
What are the mechanism, contraindications and side effects of osmotic diuretics
- M: Osmotic receptors attach onto H20 preventing it from reabsorbing.
- C: Anuria and Heart Failure
- S/E: Mg2+ loss
What are osmotic diuretics used for
Brain odema
Give an example of Carbonic anhydrase and where it acts long the nephron
- E.g. Acetazolamide
- PT and CD
What are the mechanism, contraindications and side effects of carbonic anhydrase
- M: Prevents Na+/H+ exchanger and HCO3- reabsorption
- C: Acidosis
- S/E: Metabolic acidosis
What are carboinc anhydrase use for
Glaucoma
Give an example of Loop diuretics and where it acts long the nephron
- E.g. Frusemide
- TAL
What are the mechanism, contraindications and side effects of Loop diuretics
- M: Inhibits the NKCC2 transporter by binding onto the Na+ site. Prevents the reabsorption of Na+, K+ and Cl-.
- C: Anuria
- S/E: Loss of electrolyte and uric acid secretion
What are loop diuretics use for
Oedema
Give an example of a thiazide and where it acts long the nephron
- E.g. Cholorthiazide
- DT
What are the mechanism, contraindications and side effects of Thiazides
- M: Blocks the NCC (Na+, Cl-) co-transporter. Binds onto the Cl-, therefore more Na+ arrives at the CD
- C: Anuria and Hypokalemia
- S/E: Hypokalemia and retention of uric acid
What are thiazides use for
- HT
- Oedema with good GFR
Give an example of a inhibitor of ENaCs and where it acts long the nephron
- E.g. Amiloride
- Principal cells of CD
What are the mechanism, contraindications and side effects of Inhibitors of ENaCs
- M: Amiloride competes with Na+ site on the ENaC. This blocks Na+ absorption and K+ secretion
- C: Hyperkalemia and Anuria
- S/E: Hyperkalemia and N/V
What are Inhibitors of ENaCs used for
- HT (in conjunction with other diuretics)
- Reduced the K+ loss of Loop diuretics
What is the special feature of Inhibitors of ENaCs
K+ sparing diuretics
Give an example of a Aldosterone antagonist and where it acts long the nephron
E.g. Spironolactone
CD
What are the mechanism, contraindications and side effects of Aldosterone antagonist
- M: Inhibits aldosterone from binding thus inhibiting Na+ reabsorption and K+ secretion
- C: Hyperkalemia
- S/E: Acidosis and Hyperkalemia
What are Aldosterone antagonist used for
HT and Hyperaldosteronism
What is the special feature of Aldosterone antagonist
K+ sparing diuretics
Give an example of methylxanithines and discuss its function
E.g. caffeine
No clinical use, increases GFR via pre renal mechanism
Normal pH
7.4 tightly regulated
Acidosis
<7.35
Alkalosis
>7.45
What are the three layers of protection from acids
(1) Chemical Buffering
(2) Respiratory response
(3) Kidney response
chemical buffering
Looks after excess H+ by binding it to body’s buffer bases
Respiratory response
Excess H+ is breathed out in the form of CO2
Kidney Response
Deals with acid load by dividing the acid (H2Co3-) into H+ and HCO3-. H+ gets excreted out in the urine and HCO3- re-enters the blood stream
How does kidney reabsorption and secretion of HCO3- and H+ work
Direct response: Involves secretion and reabsorption of H+
Indirect response: Involves secretion and reabsorption of HCO3-
Kidney’s during acidosis
(1) Secrete H+ by primary and secondary active transport
(2) Buffer H+ with ammonia or phosphate
(3) Make new HCO3- from CO2 and H20
Transporters involved with H+ and HCO3-
- Na+/K+ ATPase
- Na+/H+ antiporter
- Na+/HCO3-symporter
- Na+/NH4+ antiporter
- H+ ATPase channel
- H+/K+ ATPase
- HCO3-/Cl- antiporter
Titratable Acid
- Represents the amount of H+ bound to phosphate which is present in significant concentration.
- Primary urinary buffer is considered to be a titratable acid
Which part of the nephron absorbs the largest amount of HCO3-
PT followed by LOH (TAL) and DT
What’s the relationship between plasma [HCO3-] and urine [HCO3-]
Once the plasma [HCO3-] gets to it’s threshold point there is a increase in urine [HCO3-]
When is HCO3- secreted
During metabolic alkalosis
Why is HCO3- secreted during metabolic alkalosis
Want to reabsorb the H+ rather than excrete to help deal with the alkalosis. Therefore there is a decrease in new HCO3- being formed
How is new HCO3- formed
Two mechanisms:
(1) Secretion of H+ produces new HCO3-
(2) Secretion of NH4+ produces new HCO3-
Discuss the process in which secretion of H+ produces new HCO3-
Discuss the process in which secretion of NH4+ produces new HCO3-
What is the role of making NH4+
Increase the synthesis of new HCO3-
WHy is NH4+ secretion important
If NH4+ wasn’t secreted it would re-enter the blood stream and end up at the liver where it would be metabolised to make urea. Formation of urea requires two HCO3-
Urine Anion Gap
Gives a rough indication of how much NH4+ is in the body.
What are the types of renal tubular acidosis
- (1) Proximal RTA: Decrease H+ secretion –> Decrease HCO3- reabsorption
- (2) Distal RTA: Decreases H+ secretion –> Decrease excretion of titratable acid
- (3) Other RTA: Decrease in NH4+ production –> Decrease NH4+ urinary production
What does a high plasma anion gap indicate
Metabolic acidosis
What is paradoxical aciduria and which condition does it occur in
When there is a low urine pH even though the body is in metabolic alkalosis. Commonly occurs in vomiting
How does paradoxical aciduria occur
- Increase Na+ reabsorption due to volume loss
- This stimulates increase HCO3- reabsorption and H+ secretion.
- Also, increase in aldosterone, leads to increase H+ secretion
Ultrafilter
Semipermeable membrane that is used as a filter to separate small molecules and water from large molecules
Ultrafiltration
High hydrostatic pressure that forces small molecules into the filter.
Three properties of an ultra filter
Three properties of an ultra filter
- Endothelial fenestrations: “Gaps”
- Basal membrane composed of collagen and elastic: Importnat to GN
- Podocytes: Prevents large molecules going into filtrate
How does the filtrate remain clean
- Podocytes
- Mesangial macrophages
Determinants of filtration
- Pcap: Pressure that pushes fluid out of the capillaries
- Oncotic pressure: Pressure that is exerted on the fluid by proteins in the blood
- Pinterst: Compels fluid to be pushed back into the capillaries
Effective Filtration Pressure (Peff)
- Considered the net pressure of the filtration. Composed of force out - force in.
- Pcap - (osmotic + PInterst)
- Around 25 torr
What provokes auto-regulation of RBF
- [NaCl] DT - detected by the macula densa cells
- Changes in MAPr (Mean arterial pressure of kidney)
What is auto-regulation of RBF
Essentially, autoregulation stops the RBF drastically changing in response to changes in MAPr between the pressure ranges of 80-170mmHg. This is achieved due to Pcap remaining ~60 torr irrespective of changes in MAPr
Discuss how changes in MAPr evoke auto-regulation
- Tendency of SM to contract when stretched.
- increase in vessel diameter –> Leads to non selective cation channel to open –> Depolarisation occurs which leads to influx of Ca2+ and contraction
Discuss how changes in [NaCl] evoke auto-regulation
Increase in [NaCl] on DT is picked up by macula Densa cells. The rise causes the afferent arteriole in vasoconstrict.
Function of RBF
- Determines GFR
- Delivers substrates for excretion
- Delivers O2 and nutrients to renal cells
- Assist in urine concentration
In terms of GFR, RBF and Pgc, what happens with afferent vasoconstriction
- Decrease GFR
- Decrease Pgc
- Decrease RBF
In terms of GFR, RBF and Pgc, what happens with afferent vasodilation
- Increase GFR
- Decrease in Pgc
- Increase RBF
In terms of GFR, RBF and Pgc, what happens with efferent vasconstriction
- Increase GFR
- Increase Pgc
- Decrease RBF
In terms of GFR, RBF and Pgc, what happens with efferent vasodilation
- Decrease GFR
- Decrease Pgc
- Increase RBF
Vasoconstrictors
- Remember: Never Attempt Absailing Naked
- NSAIDs
- ANP
- AG II
- Noradrenaline
Vasodilators
- Remember: April Pascoe Never Associated with Assholes
- ANP
- Prostaglandin
- NO
- Ace1
- ARB
What two components determine homeostatic control
Fluid Volume
Fluid Osmolality
What is fluid osmolality
H20 reabsorption (Diluting and concentrating of urine)
What is fluid volume
NaCl reabsoprtion
What controls fluid osmolality
ADH
What controls fluid volume
RAA system
What stimulates ADH
Plasma osmolality > 300mosmol
Osmoregulation
Regulation of osmotic pressure of fluid to maintain homeostasis of H20 content
How is thirst stimulated
Stimulated with ~2-3% increase in osmolality
What stimulates the RAA system
Effective volume control (CVe)
Identify the sensors of CVe
- (1) Vascular * most important
- (2) Hepatic
- (3) CNS
What are the different responses to CVe
- (1) Local response - Response of a single nephron. Fast acting
- (2) Systemic response - Response of entire kidney. Slower acting
What is the function of Juxtaglomerular Appratus
Control the renal blood flow and glomerular filtration rate
Identify the cells of the JGA
Glomerular cells
Macula Densa cells
What is the role of glomerular cells
control the release of renin
What is the role of macula densa cells
respond to [NaCl] changes in nephron
Why do we have a systemic response to CVe
Allows our body to change the systemic volume and BP
What is the role of RAA system
Regulates the body’s BP and Volume via the action of angiotensin II and aldosterone.
What organs are involved in RAA system
- Kidney -> Makes Renin
- Adrenal Gland –> Makes aldosterone
- Liver –> Makes angiotensin
- Lung and Kidney –> Express ACE
- ACE targets –> Vessels, CNS, Kidneys and Adrenal gland
How does the RAA system work
What mechanisms are used to maintain Na+ delivery to CD
- Auto-regulation of GFR
- Glomerular tubular balance (GTB)
- Load dependency of Na+ reabsorption
Changes with hypervolumic state
- Increase ANP
- Decrease ADH
- Decrease Symp. acitivity
- Decrease renin
- Decrease Angiotensin II
- Decrease Aldosterone
Changes with hypovolumic state
- Decrease ANP
- Increase ADH
- Increase Symp.activity
- Increase Renin
- Increase Angiotensin II
- Increase Aldosterone
What prevails osmotic control or volume control
- Osmotic control > volume control
- Quicker and stronger response
