Urinary Session 9 Flashcards
Why is acute kidney injury hard to define using measured levels?
Actual GFR fluctuates normally but is largely constant whereas the creatinine peak used for staging isn’t detectable until 7 days after insult
Why is AKI a medical emergency?
Rapidly leads to renal failure
How does serum creatinine change through stages 1-3 of AKI?
1= 150-200% increase from baseline 2= >200-300% increases 3= >300 %
What causes the majority of AKI cases in the UK?
85% prerenal or ATN
What are common causes of AKI seen outside of the UK?
Infection
Diarrhoeal illness
Obstetric
Occupational e.g. Copper sulphate in the dye industry
What is acute kidney injury?
A clinical syndrome caused by an abrupt decreases in actual GFR which can be over days to weeks leading to upset of ECF volume, electrolyte and acid/base disturbance and accumulation of nitrogenous waste
What is the pathogenesis of pre-renal AKI?
Actual GFR decreases due to decreased renal blood flow
Why can the kidneys respond to pre-renal AKI and not some other types?
No cell damage
How does the kidney respond to pre-renal AKI?
Avid reabsorption of sodium and water via aldosterone and ADH release
What medications can lead to pre-renal AKI?
NSAIDs
ACEI/ARBs
How can NSAIDs cause pre-renal AKI?
Switch off prostaglandin synthesis therefore decreased afferent vasodilation and subsequent decrease in actual GFR
How can ACEI/ARBs cause pre-renal AKI?
Decrease circulating vasoconstrictors causing a decrease in actual GFR
How can DM lead to pre-renal AKI?
Causes disease of afferent arteriole –> hypersensitivity or insensitivity to stimuli so GFR cannot be maintained
What causes of decreased ECV can lead to pre-renal AKI?
Hypovolaemia due to blood/fluid loss or 3rd spacing
Cardiac failure due to LV dysfunction, valve disease or tamponade
Systemic vasodilation due to sepsis, cirrhosis or anaphylaxis
What dual action can sepsis have to contribute towards development of pre-renal AKI?
Causes systemic vasodilation and vasodilation of the efferent arteriole
What disease states can lead to impaired renal autoregulation leading to pre-renal AKI?
Pre glomerular vasoconstriction due to sepsis, hypercalcaemia, hepatorenal syndrome, NSAID Tx
Post glomerular vasodilation due to ACEI or ARBs
What is acute tubular necrosis?
When PCT cells are damaged and need replacing and are therefore not reabsorbing sodium or managing water levels effectively
Which cells are implicated in acute tubular necrosis and why?
PCT as they are most vulnerable due to their high energy demands
Why should aggressive fluid resuscitation not be used to treat acute tubular necrosis?
Damaged PCT cells cannot expel excess water so would lead to overload
Which blood vessels are implicated in ischaemia leading to ATN?
Peritubular capillaries
Why are the PCT and thick ascending limb of Henle’s loop at risk of damage from ischaemia?
Outer medulla is relatively hypoxic due to BV distribution
In ATN due to ischaemia, why are the glomerulus and distal tubules preserved?
Glomerulus receives sufficient bloody supply and the distal tubules have lower oxygen demands so also receive sufficient blood supply
How do nephrotoxins cause ATN?
Damage tubule-lining epithelial cells –> cell death and shedding into lumen
When is nephrotoxin damage much more likely to lead to ATN?
During reduced perfusion
Give some examples of endogenous nephrotoxins.
Myoglobin
Urate
Bilirubin
Give some examples of endogenous nephrotoxins which cane lead to ATN.
Endotoxin X-Ray contrast Drugs: ACEI, Aminoglycosides, NSAIDs Weed killers Antifreeze
How can sepsis cause ATN?
Exact mechanism is unknown but it combines ischaemia with endotoxin damage
How can urine biochemistry be used to differentiate between pre-renal and ATN AKI?
Pre renal: specific gravity is raised, osmolality is raised, urinary sodium is low
ATN: specific gravity is reduced, osmolality is reduced, urinary sodium is raised
Why can urine biochemistry not exclusively be used to diagnose pre-renal vs ATN AKI?
Other factors affect the ability to concentrate urine e.g. age
What type of AKI do glomerular and arteriolar disease cause?
Intrinsic
What is primary acute glomerulonephritis?
Where disease only affects the kidneys e.g. IgA nephropathy
How does secondary glomerulonephritis differ from primary?
Kidneys are involved as part of systemic process e.g. SLE, vasculitis
How does granulomatosis with polyangitis (Wegener’s granulomatosis) cause intrinsic AKI?
Walls of BV become inflamed –> rapidly progressive crescenting necrotising glomerulonephritis
What can lead to microangiopathic haemolytic anaemia causing intrinsic AKI?
Haemolytic uraemia syndrome
Malignant hypertension
Pre-eclampsia
What is the pathogensis of microangiopathic haemolytic anaemia?
Endothelial damage –> platelet thrombi –> partial occlusion of small arteries –> RBC destruction
What type of AKI can acute tubulo-interstitial nephritis lead to?
Intrinsic
What happens in acute tubulo-interstitial nephritis due to infection?
Acute pyelonephritis leads to increased spacing of functional tubules due to inflammatory cell infiltration, esp eosinophils
What are the common causes of toxin induced acute tubulo-interstitial nephritis leading to interstitial AKI?
Abx, NSAIDs, PPIs
In high-risk pts consider all drugs until prove otherwise
What proportion of AKI cases are due to obstructive AKI?
5-10%
On which population is obstructive AKI more common?
Elderly
Why must the obstruction in obstructive AKI block both kidneys or a single functioning kidney?
It is possible to survive on one kidney with the only detectable change being a slight increase in creatinine
What is the pathogenesis of obstructive AKI?
Obstruction with continuous urine production –> increased intraluminal pressure –> dilation of renal pelvis –> decrease in renal function
What is hydronephrosis?
Dilation of renal pelvis
Give some examples of intraluminal causes of obstructive AKI.
Stones, blood clots or tumour within kidney, ureter or bladder
What criteria must renal stones have to fit in order to cause obstructive AKI?
Be in both renal pelvises or ureters or be obstruction neck of bladder/urethra
>10 mm
Why will renal stones in the kidney tissue not lead to obstructive AKI?
Too small
What within-wall causes can lead to obstructive AKI, although tend to lead to CKD instead?
Congenital megaureter
Post-TB stricture
What causes from pressure outside can lead to obstructive AKI?
Enlarged prostate
Cervical/uterine tumour
Aortic aneurysm
Ligation of ureter during surgery
What four-step approach should be used for a pt with AKI?
Regulate BP and blood volume
Regulate pH, electrolytes and osmolarity
Excretion of waste inc metabolism of drugs
Endocrine function of kidney
How will a pt with AKI who is volume depleted present on examination?
Cool peripheries Fast pulse Low BP/postural hypotension Reduced JVP Decreased skin turgor Dry axillae
How will a pt with AKI who is volume overloaded present on examination?
Gallop rhythm
Increased JVP
Pulmonary oedema
Peripheral oedema (sacral/ankle)
How will a pt with AKI and sepsis present O/E?
Pyrexia Rigors Warm peripheries Bounding pulse Rapid capillary refill Hypotension
How will a pt with AKI and urinary tract obstruction present O/E?
Anuria Single functioning kidney Loin/suprapubic pain Hx of renal stones, prostatism, previous pelvic or abdominal surgery Palpable bladder Pelvic/abdominal mass Enlarged prostate Blocked catheter
What must every pt with AKI have?
Urinalysis for blood, protein and leukocytes
What do grossly elevated levels of blood and protein on dipstick analysis in AKI indicate?
Intrinsic renal AKI
How will pre-renal AKI appear on investigation?
No proteinuria or haematuria and normal microscopy
How will glomerulonephritis present on investigation in AKI?
+++ proteinuria
+++ haematuria
RBC casts on microscopy
Does ATN cause proteinuria and/or haematuria?
No
Is microscopy performed for ATN in AKI?
No
What is Rhine biochemistry used to investigate in AKI?
Osmolality and urine sodium in cases where electrolytes are severely deranged to see if this is due to the kidneys
When is an US scan performed within 24 hrs of presentation in AKI?
Suspected obstructive AKI
If pre-renal of ATN AKI doesn’t respond to Tx
Why might a CXR be used to investigate AKI?
Identifies fluid overload +/- infection
When is a kidney biopsy performed to investigate AKI?
Pre- and post renal AKI have been ruled out
+ Confident diagnosis of ATN cannot be made
+ Systemic inflammation
What are the risk factors for developing AKI?
Increasing age CKD Heart disease Liver disease DM Cancer Neurological impairment Previous AKI Dehydration Sepsis Burns Trauma Radio-iodinated contrast in last week
Why is liver disease a risk factor for AKI?
Poor blood supply to kidney
Nephrotoxic bilirubin to kidney
How can AKI be prevented?
Monitor ‘at risk’ pts closely, esp when prescribing
Ensure adequate hydration
Avoid nephrotoxins
Early detection and cause identification
How is volume overload in AKI managed?
Restrict dietary sodium and water intake to
How is hyperkalaemia in AKI managed?
Immediately: calcium gluconate Then: Restrict dietary intake Stop K+ sparing diuretics, ACEI and ARB Exchange resins Dextrose and insulin NaHCO3- if HCO3- low Beta-2 agonists
What is the effect of using beta-2 agonists to treat hyperkalaemia in AKI?
Transiently drives K+ into cells
How is acidosis in AKI managed?
Restrict protein in diet (watch out for malnutrition)
NaHCO3-
When is dialysis used to manage AKI?
Hyperkalaemia after Tx Metabolic acidosis where NaHCO3- inappropriate Fluid overload after diuretics Presence of dialysable nephrotoxin Signs of uraemia
Give examples of dialysable nephrotoxins which would indicate management of AKI with dialysis irrespective of disease stage.
Aspirin
Ethylene glycol
What are the signs of uraemia?
Pericarditis
Decreased GCS
Intractable N&V
What are the outcomes following AKI?
Uncomplicated ATN –> 2-3wk recovery if no further insults
Uncomplicated ATN with hypotension on dialysis –> more ischaemic lesions –> prolonged recovery
Increased risk of death for one year following
Increased risk of CKD
Why does any disease that affects the vasculature of the glomerulus have a downstream affect on the associated tubule?
It receives its blood supply from the efferent arteriole or the glomerulus
What are the functions of the kidney?
Excretion: water, salt, electrolytes, acid, metabolic waste
Glomerular permselecitivty
Tubular: [urine], HCO3- reabsorption, NH4+ secretion
Endocrine: 1-alpha-calcidiol, renin, erythropoietin
Does a pt presenting with pain indicate glomerulonephritis of diabetic nephropathy?
No these are painless. Indicates stones or back pain
Can urinary appearance be used to identify renal disease?
No, too variable
Does urinary flow disturbance indicate renal disease?
No, often due to urological disturbance
What are the sequelae of impaired kidney excretion?
Hyperkalaemia Sodium and water overload Acidosis Metabolic waste products in blood Uraemia syndrome
What died the rate of excretion by the kidney depend on?
Rate of filtration
What are the sequlae of impaired glomerular permselectivity?
Proteinuria
Haematuria
What is the earliest indication of kidney disease?
Impaired urine concentrating ability leading to frequency and nocturia
What can impaired tubular function in kidney diseases contribute to?
Acidosis
Why is glycosuria seen with normal blood glucose in impaired tubular functions?
Renal glucose threshold is lowered
How can the effect of impaired tubular function on renal glucose threshold be used to Tx DM?
SGLT2 inhibitor causes lowering of renal glucose threshold so more is lost in the urine
What are the sequelae of impaired endocrine function of the kidneys in renal disease?
Vitamin D not activated –> metabolic bone disease
Decreased erythropoietin –> renal anaemia
Decreased renin –> hypertension
What do the S/S of renal disease depend on?
Speed of onset
Which pts are routinely scanned for kidney disease due to asymptomatic nature?
Hypertensive Heart disease DM Urinary tract obstruction Systemic disease e.g. Myeloma or lupus
What is the most common cause of microscopic haematuria?
UTI
Give some examples of causes of microscopic haematuria.
Polycystic kidneys Renal stones Tumours Arteriovenous malformations Kidney/glomerular disease
What do pts >45 y.o. require as primary investigation following detection of microscopic haematuria?
Cystoscopy
How does blood form the top of the glomerular pathway present in macroscopically haematuria?
Red urine throughout stream
If blood in macroscopic haematuria clots, where is it likely to be from?
Bladder or tumour, not glomerulus
Where is blood at the beginning or end of stream likely to be from?
Ureters or bladder
What does macroscopic haematuria need to be distinguished from?
Haemoglobinuria
Myoglobinuria
Food dyes
What is the most common cause of glomerular haematuria?
IgA nephropathy within 24 hours of URTI
Is glomerular haematuria painful?
No usually painless
What might be seen on investigation of glomerular haematuria and why?
Dysmorphic RBCs due to squeezing through glomerulus
Red cell cast as decreased flow/increased [salt]/decreased pH favour Tomm-Horsfall microprotein secretion by renal tubule cells
Is Tomm-Horsfall microprotein secretion by tubular cells always pathological?
Yes
How does proteinuria present?
Frothy urine
What are the sequelae of significant amounts of protein loss via the urine?
Oedema due to albumin loss
Infection due to immunoglobulin loss
Prothrombotic state due to coagulation cascade protein loss
What is the classic triad of findings in nephrotic syndrome?
Proteinuria which is significant enough to cause hypoalbuminaemia and oedema
What additional finding is seen in nephrotic syndrome as well as the classic triad?
Hyperlipidaemia due to liver function disturbance
What is the classic triad of nephrotic syndrome pathognomonic of?
Glomerular disease needing renal biopsy to determine cause
What is the cause of all nephrotic syndrome presentations?
Disruption of fort processes of podocytes in the glomerular permselectivity membrane
What is the clinical presentation of a pt with nephrotic syndrome?
Swelling around face (but able to lay flat)
Horizontal crescents on fingernails (Muehrcke’s bands)
Xanthelasma
Fat bodies in urine
Unilateral swollen leg due to oedema and DVT
What is classic nephritic syndrome?
Post-streptococcal glomerulonephritis in children
Why is classic nephritic syndrome not now commonly seen in the UK?
Abx
What are the S/S of rapid onset nephritic syndrome?
Oliguria Hypertension General oedema Haematuria Normal serum albumin Variable renal impairment Urine with blood, protein and cell casts
What is needed to diagnose nephritic syndrome?
Biopsy to identify different ultra structural damage to nephrotic syndrome
How does nephritic syndrome compare to nephrotic syndrome?
Faster onset, less oedema, raised BP, raised JVP, less proteinuria, more haematuria, red cell casts are present and serum albumin is NOT lowered
What is rapidly progressive glomerulonephritis?
Clinical situation where severe glomerular injury different to nephrotic and nephritic injury causes decreased renal function over days
How might a pt with rapidly progressive glomerulonephritis present?
Uraemia emergency with evidence of extra-renal disease due to systemic cause
What is rapidly progressive glomerulonephritis associated with?
Crescentic glomerulonephritis
Anti neutrophil cytoplasmic antibodies
Anti glomerular BM antibodies
Systemic vasculitis
On what imaging is systemic vasculitis visible?
CXR
CT scan
What is the commonest cause of kidney disease?
CKD
Describe the progression of CKD?
Slow, pts don’t present until GFR sob, N+V, aches+pains, sleep reversal, nocturia, restless legs, itching, chest pains –> seizures and coma
