Renal replacement and drugs Flashcards
What are the 6 classses of diuretics
Osmotic diuresis
Carbonic anyhydrase inhibitors
Aldosterone antagonists
ENaC channel antagonists
Loop diuretics
Thiazide diuretics
What is an osmotic diuretic? What are 2 side effects? How does it work?
- Mechanism - unresorbable but fully filtered solute acts by increasing the osmolarity of the tubular fluid and therefore reducing the osmotic gap between fluid and intersititum; thereby reducing the effect of urine concentration mechanisms as fluid is not able to effectively move out of the tubule down a concentration gradient
- Example: Mannitol
- Side effects:
◦ Hypotension
◦ Hypokalaemia
Where do carbonic anhydrase inhibitors work? What is their mechanism> Side effects?
- Site: proximal convoluted tubule
- Mechanism: Block the enzyme carbonic anhydrase on PCT cell surface and within PCT cells
◦ Decreased re-absorption of bicarbonate and sodium increasing tubular fluid and osmolality - Example: acetazolamide
- Side effects
◦ Metabolic acidosis
◦ Hypokalaemia
Where do loop diuretics act
sodium-chloride-potassium cotransporter inhibition in the thick ascending LOH
What is the MOA of loop diuretics?
Disruption fo the counter current multiplier system by decreasing absorption of ions from the loopof Henle into the medullary intersittium thereby decreasing the osmolarity fo the medullary intersitital fluid and its concentration ability, in addition to impairing reabsorption fo sodium the key determinant of fluid osmolality
What are side effects of loop diuretics
◦ Hypotension
◦ Hypokalaemia
◦ Metabolic alkalosis - hypochloraemia
Thiazide diuretics site of action and mechanism
- Site of action: DCT sodium and chloride co-transporter
- Mechanism of action: sodium and chloride transporter inhibition increasing sodium delivery to the distal nephron, preventing reabsorption of urinary water by reducing the tubulo-medullary osmotic gradient
What are side effects of hydrochlorothiazide
- Side effects: hypokalaemia, hyponatraemia, gout flares, vasodilation
Aldosterone receptor antagonists act where? WHat is the MOA?
- Site of action: Collecting duct + DCT
- Mechanism of action: block aldosterone receptors
◦ Leads to reduced ENaC channel expression, reduced Na/K exchange on basolateral surface and reduced hydrogen ion secretion in the DCT leading to reduced sodium reabsorption and higher tubular sodium content
What are side effects of aldosterone antagonsits
◦ Hyponatraemia
◦ Hyperkalaemia
◦ Metabolic acidosis - Type 4 RTA
◦ Gynaecomastia
What are non aldosterone receptor antagonists? MOA? Side effects?
- Site of action: ENaC channel blockade
- Mechanism of action: Reduced sodium reabsorption, therefore reduced tubulo-medulary osmotic gradient
- Example: Amiloride
- Side effects: hyponatraemia, hyperkalaemia
Define dialysis
is the separation of particles in a liquid based on their ability to pass through a membrane - this process occurs through filtration and diffusion.
What is haemofiltration? What is it based on?
How is ultrafiltration manipulated
◦ Positive pressure is increased in blood through blood pump increasing flow through the dialyzer; but additionally return pressure as seen below if elevated will increase clearance also
◦ Negative pressure applied to the dialysate side by the machine
What is transmembrane pressure? How would you calculate it?
Convective flux means what?
Equation
the mechanism by which solutes pass through the membrane is haemofiltration
= ultrafiltration rate x solute concentration in plasma x sieving coeffcient
What is a sieving coefficient
Ratio of specific solute concentration in ultrafiltration/mean plasma concentration in the filter
What are the factors affecting clearance in haemodialysis
- Pressure difference - primary control variable
- Permeability of the dialysis membrane and resistance to flow
- Oncotic pressure difference - not maniuplated
- Reflection coeffiicient
What is the equation determining flow in haemodialysis
Fick’s law
Define diffusion
spontaneous movement of substances from a higher solute concentration to a lower solute concentration
What enhances the efficacy of dialysis mechanisms rather than haemofiltration mechanisms
Countercurrent
Each substances clearance by haemodialysis is governed by
◦ Each substance’s clearance will be a reflection of
‣ Concentration difference - increased difference increases clearance, which can be manipulated through reduced concentrations in dialysate fluid of substances to be cleared; and is maximised through countercurrent flow of dialysate fluid
‣ Individual solute characteristics e.g. molecular weight, shape/size and charge will influence
Total clearance in haemodialysis is a function of?
Increasing surface area —> increased clearance and vice versa
‣ Reduced thickness of membrane —> increased clearance
‣ Porosity of the membrane
‣ Increased temperature
How is blood flow through a dialysis circuit determined
- Blood flow (Q) = (Pa-Pv)/R
◦ Pa = access pressure
◦ Pr = return pressure
◦ R = circuit resistance
What factor affects access and return pressure in a dialysis circuit?
◦ Set blood pump speed
◦ Vascular access device properties
◦ Pressure at access points - arterial, central venous pressure
When describing resistance in a dialysis circuit what factors are important
As resistance is occurnig within a set of tubing it is determined to an extent by Hagen Pouseulle equation
- Resistance = 8nL/πr4 where
◦ n = viscosity,
‣ 3.5 - 5.5 cP and depends on
* Haematocrit
* Blood protein and lipid content
* Temperature
* Pre and post replacement fluid
* Fahraeus Lindquist effect where blood becomes less viscous in smaller vessels (<0.5mm diamtre) because of RBC deformation
◦ π = 3.14,
◦ r = radius
‣ vascular access
‣ filter deisgn
‣ Circuit dimensions
‣ Clot or fibrin
‣ Anticoagulant strategy
◦ L = length - generally 3.5m
What is the Limitation of using a Hagen Pousieulle equation to describe resistance in a dialysis circuit?
Blood vessels are elastic and contrcatile rather than rigid tubes
Blood flow often turbulent within dialysis machines
Poisuelles law is constant flow - this is pulsatile
Blood is a non newtonian fluid
What are the two mechanisms of fluid removal in a dialysis machine
- Osmosis
- Ultrafiltration
How does osmosis work in a dialysis machine
◦ Movement of FLUID (solvent) across a semipermeable from an area of LOWER solute concentration to an area of HIGHER solute concentration.
◦ When a solvent passes through a membrane, the process is called osmosis. (semipermeable)
Solute removal mechanisms in a dialysis machine?
Diffusion
Convection
What is convection in reference to dialysis?
◦ Osmosis is when a solvent passes through a membrane. The frictional forces between solutes and water molecules will pull dissolved substances along, a process known as bulk flow or solvent drag.
◦ Important for movement of small solute (urea, creatinine). Elimination via bulk flow is independent of solute concentration gradients across membranes
◦ Transport dependent on Starlings forces
‣ Transmembrane pressure determined by blood flow to the membrane and oncotic pressure; and flow is subsequently influenced by porosity
When does renal dysfunction result in clinical symptoms - what % of loss
50-75% of function must be lost as existing nephrons excrete additional water and electrolytes increasing their filtration and reabsorption