Renal Therapeutics II Flashcards
Define: Acute renal failure (ARF)
Rapid, potentially irreversible decline in renal function (GFR) occurring over hours or days
Define: Chronic renal failure (CRF)
Slowly worsening loss of the ability of the kidneys to:
Remove wastes
Concentrate urine
Conserve elctrolytes
List the stages of renal failure
- Normal GFR with other evidence of chronic kidney damage
- Mild impairment, decreased GFR
- Moderate impairment, decreased GFR
- Sever impairment, decreased GFR
- Established renal failure (ERF) =
What classes as ‘other evidence of chronic kidney damage’ which diagnoses an individual with the 1st stage of renal failure?
Persistent microalbuminuria = albumin in urine Persistent proteinuria = abnormal quantities of protein in the urine Persistent haematuria (after exclusion of other causes) = presence of blood in urine Structural abnormalities revealed by ultrasound Biopsy-proven glomerulonephritis = damage to the glomeruli
List 3 types of causes of renal failure
Pre-renal cause/failure = consequence of decreased renal perfusion –> reduction in GFR
Intrinsic renal cause/failure = e.g. damage to nephrons
Post-renal cause/failure = beyond the kidney e.g. obstruction to urine flow
What causes glomerular dysfunction?
Pre-renal perfusion
Intrinsic glomerular inflammation = problems with liquid being able to pass through
Post-renal obstruction
What are the consequences of glomerular dysfunction?
Fall of GFR with retention of substances that should be cleared by filtration
So:
Reduced volume of tubular fluid and urine
Slower tubular flow
Increased tubular reabsorption
This can cause proteinuria and increased protein loss
What is the function of the tubules?
Selective reabsorption of water, electrolytes etc.
What are the consequences of tubular dysfunction?
Polyuria and loss of electrolytes
Which 3 areas of the nephron can suffer from tubular dysfunction?
Loop of Henle
Proximal convoluted tubule
Distal convoluted tubule
What is the result of a failure of the Loop of Henle?
Urine cannot be concentrated (missing medulla gradient)
What is the result of proximal tubular failure?
Potassium loss
What is the result of distal convoluted failure?
Impaired Na-K acid exchange pump,
So failed acid secretion (body cant get rid of acid through the urine) = acidosis = decreased pH in bloodstream
Define: Nephrotoxic effect
Poisonous effects of some substances on the kidneys
Name 2 drugs that can cause glomerulonephritis (damage to glomeruli)
Penicillamine
Gold
Name 2 drugs that can cause an alteration in renal blood flow
RAAS inhibitors
NSAIDs
What can cause obstruction in the kidneys?
Crystallisation of drugs = crystalluria
Prevents liquid flowing through
Describe the typical time course of acute renal failure if it has a pre-renal cause
Pre-renal cause
GFR decreased, oliguria (small amounts of urine)
Acute tubular necrosis
Oliguric phase = glomerular and tubular dysfunction
Polyuric phase = persistent tubular dysfunction
Recovery period
What causes the oliguric phase in ARF?
Low GFR = Acute tubular necrosis = Glomerular dysfunction = Oliguric phase = Reduced clearance, fluid and electrolyte retention
What occurs during the polyuric phase of ARF?
The glomeruli have recovered but tubular dysfunction still exists
Filtration is increasing but concentration mechanisms do not work so still causing issues
= large volume of urine produced
What occurs during the recovery phase of ARF?
The tubule cells slowly regenerate
Kidneys recover their own function and regenerate
What are the clinical features of the oliguric phase of ARF?
Fluid and electrolyte overload Accumulation of metabolites = Infections, bleedings and = Problems related to volume overload = hypertension, oedema
What are the clinical features of the polyuric phase of ARF?
Dehydration
Electrolyte depletion
= Volume depletion = nausea, vomiting, muscle cramps
Describe the management of ARF
No specific management for ARF
Remove cause
Keep patient alive until kidney functions have recovered (maintain fluid and electrolytes)
Dialysis helpful
How is restoration of function achieved after pre-renal failure?
Fluid or blood replenishment
Restoration of CV function
Prevent acute tubular necrosis
This may require aggressive dialysis therapy
Which 2 groups of drug are commonly used in order to restore function after pre-renal failure?
Calcium-channel blockers = dilate glomerular arterioles (=more blood to kidney), induce natriuresis (excretion of sodium in urine)
Diuretics = block normal solute reabsorption
Describe how thiazides (diuretics) work to restore function after pre-renal failure
Block Na & Cl reabsorption in the distal tubule
However K excretion increases = hypokalaemia
Reduced calcium excretion
Increases urine volume
Describe how Loop diuretics work to restore function after pre-renal failure
Block Cl, Na & K reabsorption in the LoH (mainly ascending)
Side effect = potassium loss
Give an example of a loop diuretic
Furosemide
Describe how potassium sparing diuretics work to restore function after pre-renal failure
Block Na/K exchange pump (DCT/CD)
= Natriuresis (excretion of Na in urine)
= Increased water excretion and decreased K excretion
Describe how osmotic diuretics work to restore function after pre-renal failure
Act on PCT
Filtered by the glomerulus and blocks water reabsorption in the whole nephron
Side effect = increased extracellular volume before producing diuresis
Give 2 examples of osmotic diuretics
Mannitol
Sorbitol
Define: Diuresis
Large volume of substances present
= Excessive volume of urine produced
How do thiazides treat hypertension?
Increased urine flow = reduction in plasma volume = decreased cardiac output = lower BP
What is a side effect of thiazides?
Increased potassium excretion = hypokalaemia
Do thiazides affect the GFR?
No GFR stays the same
How do thiazides prevent kidney stones
Reduced excretion of calcium = stops build up of calcium in the kidney
What should thiazides be taken in conjunction with
Potassium-sparing diuretics to prevent hypokalaemia
In which situation are loop diuretics the most suitable treatment for a patient?
For those with blood volume overload
Greatly increases GFR and so liquid flow into the kidneys = large volume of urine
How do loop diuretics have their effect?
They are actively secreted in the proximal convoluted tubule
List 3 consequences of using loop diuretics
Hypokalaemia
Increased Ca and Mg excretion
Hyperglycaemia
What is the main indication of loop diuretics?
Oedema of the lung
Anuria (failure of kidneys to produce urine)
Poisoning
As loop diuretics can greatly increase GFR = large volume of urine
List 2 side effects of potassium-sparing diretics
Hyperkalaemia
Slight acidosis
Give an example of a potassium-sparing diuretic
Spironolactone
Which is the most potent diuretic?
Loop diuretics
How do osmotic diuretics work?
Prevent water being reabsorbed throughout the entire nephron by sitting on tubule walls
What is the result of taking osmotic diuretics?
Excretion of large volume of electrolyte-poor urine
How is acidosis caused and treated?
Kidney unable to excrete H+
Therefore give sodium bicarbonate or calciumgluconate
When is dialysis used?
If patient has:
Persistent oliguria or ATN
Rising urea, potassium or creatinine levels
What is Chronic Renal Failure (CRF) usually caused by?
Intrinsic renal diseases (glomerular origins)
List 4 causes of CRF
Glomerulonephritis
Diabetes
Hypertension
Drug nephrotoxicity
List 4 common problems associated with CRF
Sickness
Tiredness
Hypertension
Polyuria
Describe the timecourse of CRF
Diagnosis
Monitoring (creatinine levels)
Careful management
May delay end stage renal failure (ESRF)
How does CRF cause kidney shrinking?
Fewer nephrons working
= Hyperfiltration
= Glomerular sclerosis (hardening), tubular atrophy (wate away)
= Kidney shrinking
What causes the fluid and electrolyte imbalance in CRF?
Initially: dilute polyuria = dehydration, electrolyte depletion
Later stage: urine volume drops so retention of sodium and water = hypertension, hypervolaemia, oedema, heart failure
What is uraemia?
Urea in the blood
Co-accumulation of electrolytes and toxins
Urea levels = indicator of toxin level
How does CRF cause anaemia?
Caused by damage to peritubular cells
= Decreased secretion of erythropoietin (hormone)
= Red cell proliferation and differentiation in bone marrow
= Haemoglobin levels decrease
= Ability of blood to carry oxygen is decreased
Define: Anaemia
Deficiency of RBCs or haemoglobin in the blood = ability of blood to carry oxygen is decreased
How does CRF cause proteinuria?
Results from:
Glomerular leaks - protein can enter tubular fluid
Infection
Failure of protein reabsorption
How can CRF cause cardiovascular disease?
Hypertension results from fluid retention and renin/angiotensin abnormalities
How can CRF cause renal bone disease (renal osteodystrophy)?
Disturbed calcium and phosphate mechanism = vitamin D deficiency Results in: Impaired bone mineralisation Bone demineralisation Deposition of calcium phosphate
What physical signs are there of renal osteodystrophy?
Rickets (lack of vitamin D)
Bones soften due to decreased calcium levels = bowed legs and possible fracture
Describe the management of CRF
Early detection
Identification and removal of cause
Preparations for renal replacement therapy
How are fluids and electrolytes managed in CRF
Water restricted to urine output + 500ml
Salt and potassium restriction
Acidosis = sodium bicarbonate or calcium bicarbonate
How should anaemia be managed in CRF?
No response to iron or folic acid in CRF
So treat with red blood cell transfusions
How should hypertension from CRF be treated?
Fluid control ACE inhibitors Beta-blockers Diuretics Calcium-channel blockers
