Week 5 - CKD Flashcards
How is H+ gained in tubular system?
- From CO2 in tissue
- Metabolism of protein and organic molecules
- Loss of bicarbonate in diarrhoea
- Loss of bicarbonate in urine
How is H+ gained in the tubular system?
- H+ + HCO3- –> H2O + CO2
- Utilisation of H+ in metabolism or organic anions
- Loss of H+ in vomitus
- Loss of H+ in urine
What are the 3 ways pH is maintained?
- Buffers
- Ventilation
- Renal H+ and HCO3- regulation
How do kidney regulate H+?
What happens during alkalaemia and acidaemia?
- H+ excretion or reabsorption
- Regulation of plasma HCO3-
Alkalaemia = low H+ = kidneys inhibit H+ excretion, increase HCO3- excretion in urine
Acidaemia = high H+ = kidneys increase H+ excretion in urine, add new HCO3- to blood
What happens in the tubules to allow no net gain of HCO3-?
HCO3- = reabsorbed in proximal tubule
1 HCO3- absorbed = 1 HCO3- filtered
HCO3- also reabsorbed in thick ascending limb
What is the process of ammonium trapping?
- NH4+ produced and secreted by proximal epithelium
- NH4+ reabsorbed at thick ascending limb, into medullary interstitium
- Exists as NH4+ and NH3
- NH3 diffuses into lumen of collecting duct
- NH3 + H+ –> NH4+ –> excreted
What happens when HCO3- is added to the blood?
- H+ secretion
- urine NH4+ concentration
- urine H2PO4- concentration (because + HPO4 required as immediate buffer for increase in H+ secretion)
What effect does aldosterone have on pH?
Stimulates H+ secretion
+ HCO3-
Aldosterone excess = leads to metabolic alkalosis
How do kidneys compensate for respiratory acidosis and alkalosis?
Acidosis = new HCO3- in blood = +NH4+ and H2PO4- in urine = acidic urine
Alkalosis = + HCO3- excretion, - H+ excretion = alkaline urine = + HPO4, - H2PO4-
What is the renal compensation for metabolic acidosis?
Kidneys = act with lungs if not source of problem
Hyperventilation
- Lungs shed H+ and put new HCO3- in blood
- Causes acidic urine
- H2PO4- and NH4+
What is the renal compensatino for metabolic alkalosis?
What are the renal actions of osmotic diuretics?
When are they used?
- Freely filtered at Bowman’s capsule
- Increase osmolality of tubular fluid in proximal convoluted tubule and loop of Henle
Use = cerebral oedema
What are the renal actions of loop diuretics?
When are they used?
- FUROSEMIDE
- +++ powerful diuretic –> peeing buckets
- Block Na+/2Cl-/K+ symporter in thick ascending limb
- Prevent creation of hypertonic interstitium so reduce ability of loop to concentrate urine
- Na+ delivery to distal convoluted tubules - loss of K+
- Decrease Na+ entry into macula densa = renin release
- Loss of transepithelial potential - reduced catino absorption
Use = chronic heart failure and renal failure
What are the renal actions of thiazides?
When are they used?
- Powerful
- Act on distal convoluted tubule
- Inhibit active Na+ reabsorption and accompanying Cl-
- solute in tubular fluid = decreased H2O reabsorption gradient
- So + H2O in tubular fluid
- Reduce circulating volume
Use = hypertension and mild/moderate heart failure
What are the renal actions of aldosterone receptor antagonists?
- Prevent Na+ pump insertion and Na+ channel insertion
- Used in primary and secondary hyperaldosteronism
- Low dose used in CHF to block aldosterone actions on heart
What are the renal actions of amiloride?
- Sodium channel blocker
- Block luminal Na+ channels in late distal convoluted tubule and collecting ducts
- Na+ not retained at K+ expense
What are the consequences of diuretics?
- Hypokalaemia - K+ loss secondary to loop diuretics and thiazides
- Leads to cardiac arrhythmias and potentiates action of digoxin
- Due to RAAS activation
- Alkalosis - H+ loss due to Na+ delivery to distal convoluted tubule
What causes hyponatremia and hypernatremia?
Hypo = Na+ < 135 mmol/L
- H2O retention secondary to excretion defect
Hyper = Na+ > 145 mmol/L
- H2O loss and impaired thirst
- Na+ retention
What is the role of K+ in renal?
- K+ affects membrane potential
- Intracellular K+ affects protein and glycogen synthesis
- K+ = redcued sensitivity to ADH
What physiological factors affects K+ transcellular distribution?
- Na+/K+ ATPase
- Insulin = + K+ intake into cells to activation fo Na+/K+ ATPase
- Catecholamines = + K+ uptake = + Na+/K+ ATPase activation
- Plasma K+ concentration
- Exercise = + K+
What are the consequences of Hypokalaemia and Hyperkalaemia?
Hypo:
- Muscle weakness / paralysis
- Cardiac arrhythmias
- Rhabdomyolosis
- Renal dysfunction
Hyper:
- Muscle weakness / paralysis
- Cardiac arrhythmias
What are the treatments for hypo and hyperkalaemia?
Hypo = KCl and HCO3- oral or IV
Hyper = Antagonism of membrane actions, + K+ entry into cells with insulin + glucose and removal of excess K+ with diuretics or dialysis
What are the properties of somatic pain?
- Pain arising from skin
- modalities
- Sensitive, well-localised, sharp pain
- Many sensory receptors
What are the properties of visceral pain?
- Fewer sensory endings in viscera
- Iften in smooth muscle
- Poorly localised
- Dull, heavy pain
- May be referred
- Pain not from harm, just overstretching or contraction
What are the properties of visceral autonomic afferent fibres?
- No peripheral synapse
- Join spinal nerve and enter CNS along dorsal nerve root
- Cell body in dorsal root ganglion
- T1-L2 = sympathetic motor outflow
- S2-4 = sacral parasympathetic outflow
Where do you feel pain with problems with the following organs?
What happens during enterohepatic recirculation?
- Drug excreted in bile
- Drug travels to GI tract
- Drug reabsorbed
- Drug travels to liver
- Process repeats
What drugs should you avoid when breastfeeding?
- Anticancer drugs
- Amiodarone
- Lithium
- Iodine containing radiocontrast media
- Tetracyclines
What are the 3 processes of renal handling of drugs?
Glomerular filtration
Active secretion
Passive reabsorption
What happens during glomerular filtration?
- Unbound drug and metabolites freely filtered
- Protein-bound drug not filtered
What are the 2 main drugs to remember that are actively secreted?
What is a key drug interaction to remember?
Uric acid
Methotrexate
Thiazides
NSAIDs block excretion of methotrexate
What happens during passive reabsorption?
- Tubule acts as lipid barrier
- Reabsorption depends on pH, pKa and lipid solubility
- Acid drugs are alkaline when ionised and vice versa
- Can be used in overdose
What determines oncotic pressure?
What is nephrotic syndrome?
Albumin
Caused by low albumin - low oncotic pressure - + interstitial fluid from + hydrostatic pressure
