Renal Therapeutics II Flashcards by Amy Lockyer

Define: Acute renal failure (ARF)

Rapid, potentially irreversible decline in renal function (GFR) occurring over hours or days

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Define: Chronic renal failure (CRF)

Slowly worsening loss of the ability of the kidneys to:
Remove wastes
Concentrate urine
Conserve elctrolytes

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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) =

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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

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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

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What causes glomerular dysfunction?

Pre-renal perfusion
Intrinsic glomerular inflammation = problems with liquid being able to pass through
Post-renal obstruction

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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

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What is the function of the tubules?

Selective reabsorption of water, electrolytes etc.

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What are the consequences of tubular dysfunction?

Polyuria and loss of electrolytes

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Which 3 areas of the nephron can suffer from tubular dysfunction?

Loop of Henle
Proximal convoluted tubule
Distal convoluted tubule

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What is the result of a failure of the Loop of Henle?

Urine cannot be concentrated (missing medulla gradient)

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What is the result of proximal tubular failure?

Potassium loss

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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

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Define: Nephrotoxic effect

Poisonous effects of some substances on the kidneys

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Name 2 drugs that can cause glomerulonephritis (damage to glomeruli)

Penicillamine

Gold

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Name 2 drugs that can cause an alteration in renal blood flow

RAAS inhibitors

NSAIDs

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What can cause obstruction in the kidneys?

Crystallisation of drugs = crystalluria

Prevents liquid flowing through

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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

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What causes the oliguric phase in ARF?

Low GFR 
= Acute tubular necrosis 
= Glomerular dysfunction 
= Oliguric phase 
= Reduced clearance, fluid and electrolyte retention

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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

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What occurs during the recovery phase of ARF?

The tubule cells slowly regenerate

Kidneys recover their own function and regenerate

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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

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What are the clinical features of the polyuric phase of ARF?

Dehydration
Electrolyte depletion
= Volume depletion = nausea, vomiting, muscle cramps

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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

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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 ```