Lecture 45a: AKI Pathophysiology Flashcards
what is the clinical relevance of AKI
- common, expensive, potentially fatal
- affects up to 25% of hospitalised Px
- prolongs hosp stay
- assc. w/ premature mortality
- linked to more rapid progression of CKD
79 year old man is admitted with cough, fever ( 38.7) and SOB.
Past history of High BP and arthritis - takes ramipril and ibuprofen.
On admission BP is 120/170 , heart rate is 109 , respiratory rate is 24 and oxygen saturation is 91%.
Blood tests showserum creatnine = 130
Diagnosed with pneumonia.Treated with antibiotics.
After 24 hours he is confused, Bp is 90/60 , creatinine is 300 and only produced 300 ml urine in 24 hr.
What is wrong with him
AKI as a result of sepsis and hypotension from pneumonia
what standardised system of assessment is always used to assess acutely ill Px in hospital
NEWS2 chart
National Early Warning Score 2
what measurements does NEWS2 chart rely on
- resp rate
- O2 sats
- BP (systolic)
- pulse rate
- level of consciousness
- temperature
what does an increase in NEWS2 score of a Px indicate
deterioration (the higher the ^ the greater the significance)
79 year old man is admitted with cough, fever ( 38.7) and SOB.
Past history of High BP and arthritis - takes ramipril and ibuprofen.
On admission BP is 120/170 , heart rate is 109 , respiratory rate is 24 and oxygen saturation is 91%.
Blood tests showserum creatnine = 130
Diagnosed with pneumonia.Treated with antibiotics.
After 24 hours he is confused, Bp is 90/60 , creatinine is 300 and only produced 300 ml urine in 24 hr.
He is diagnosed w/ AKI as a result of sepsis and hypotension from pneumonia.
How could AKI have been prevented
- recognise Px at risk of AKI because of the sepsis (pneumonia)
- review medication –> stop/avoid ‘bad’ drugs for kidney function
- ensure adequate hydration
how can renal function be measured
- measure urine volume
- measure serum creatinine
- estimating GFR
where would urine volume measurement be obtained from
fluid balance chart
how might urine output measurement be presented
- urine output per unit time
- -> total 24 urine volume
- -> urine output per hr
- -> urine output per Kg per hr (ICU)
how is serum creatinine measurement obtained
from U&E blood test
how might GFR measurement be obtained
from serum creatinine measurement (using formula - estimation)
what is the most clinically useful biomarker of kidney function
serum creatinine
at what GFR % do serum creatinine levels rise outside normal range for adult
~ below 50%
what is normal GFR in young adults
~100mL/min
what eGFR based on
formula derive from:
- age
- gender
- ethnicity
- serum creatinine
give an alternative biomarker used for eGFR other than creatinine
cystatin C
what biomarkers for eGFR might be used to get an even more accurate reading. in special circumstances
- inulin or lehoxol clearance
- radio-isotope clearance e.g. 51Cr-EDTA
what is AKI
acute kidney injury
- dec. in GFR which occurs within hours to weeks and is potentially reversible
how can AKI be recognised (simply)
- deteriorating NEWS2 score
- -> Px at risk of AKI
- rising serum creatinine
- -> automatic laboratory e-alert for AKI
- falling urine output
- -> clinical team reviewing fluid balance
what is the relevance of AKI
gives an indication that there is a problem but may not be the cause, there could be a problem elsewhere in the body
- important to look at all physiological systems to find the problem
what 3 things does normal kidney function depend on
- perfusion w/ adequate pressure and O2
- intact nephrons
- free urinary drainage
what is pre-renal AKI
disordered perfusion of a kidney which is structurally normal
what is renal AKI
damage to nephrons (glomeruli +/- tubules) often after prolonged pre renal insults
what is post renal AKI
urinary drainage obstructed
what is pre renal AKI often assc.
shock
give types of shock
- distributive (generalised vasodilatation) e.g. sepsis, anaphylaxis
- hypovolaemic (loss of circulating blood volume) e.g. internal/external loss of blood/plasma/GI fluids
- cardiogenic (pump failure) e.g MI, cardiomyopathy, arrhythmia, valvular HF
- obstructive (mechanical interference w/ blood flow) e.g. pulmonary embolism, cardiac tamponade, tension pneumothorax
what is the least common form of shock
obstructive
what is the most common type of shock
distributive
how does hypovolaemic shock lead to emerging AKI
- hypovolaemia
- hypotension
- glom cap pressure falls
- GFR falls
- less filtrate entering PCT
- develops low GFR
- emerging AKI b/c of hypotension
explain the physiological auto regulation of glomerular blood flow when less glomerular filtrate enters the tubules as a result of hypotension
- much less solute going through tubular lumen
- macula densa sense that there’s much less solute
- macula densa signal JGA
- JGA release renin –> ang2
- ang2 is potent vasoconstrictor of efferent arteriole
- vasodilation of afferent arteriole by PGs; opens
- two arterioles change resistance to restore glom cap pressure and GFR towards normal
- aldosterone acts on CD to ^ reabsorption of Na and H2O to try and restore blood volume
(regulation between tubules and glomeruli)
in pre renal AKI what are the responses to reduced perfusion
- activation of RAAS
- ^ in ADH (vasopressin) due to fall in BP
what are the features of pre renal AKI
- ^ tubular Na+/ H2O reabsorption (renal compensation for hypo perfusion)
- -> ^ urine osmolality (>500 mOsm/Kg)
- -> ^ urine specific gravity (>1.020)
- -> dec. urine [Na+] (<20mmol/L)
- -> reduced fractional excretion Na+
83 year old man has history of vomiting and diarrhoea. On examination he is restless, respiratory rate is 25 , oxygen saturation is 96%, pule is 123 , BP is 86/74, temperature is 37 and he is alert.
On admission his serum creatinine is 356, two weeks ago it was 98.
What biochemical feature is likely to be present ? A) high fractional excretion of sodium b) high urine magnesium concentration c) high urine osmolality d) high urine sodium concentration e) low urine specific gravity
c) high urine osmolality
- has pre renal AKI due to hypotension 2nd to GI fluid losses
- RAAS activation and release of ADH will result in formation of urine w/ low Na+ conc, ^ specific gravity and ^ urine osmolality
what is a consequence if there is a delay in getting a Px to hospital if they have pre renal AKI
renal AKI due to acute tubular necrosis
what consequence occurs to the cells as a result of impairment of blood flow and O2 supply to the kidney
cell injury/death
- many structures in kidney extremely sensitive to ischaemia and hypoxia
how would acute tubular necrosis normally present histologically
- hard to define normal tubular lumen
- lumens blocked by cellular debris
- quite a few cells have dies
- no nuclei (disintegrated)
what are some of the major causes of acute tubular necrosis (ATN)
- renal ischaemia followed by reperfusion
- -> severe pre renal AKI from all causes esp hypotension w/ sepsis or during surgery
- exposure to nephrotoxins
- -> drugs
- -> radiocontrast dye
- -> heme pigments e.g. myoglobin
give the features of renal AKI due to ATN
- reduced tubular Na+/H2O reabsorption (tubular damage)
- -> dec urine osmolality (<350 mOsm/Kg)
- -> dec urine specific gravity (<1.010)
- -> ^ urine [Na+] (>40mmol/L)
- -> ^ fractional excretion Na+
- reduced tubular K+ secretion
- -> ^ serum [K+] - hyperkalaemia
- reduced tubular H+ secretion and reduced HCO3- production
- -> metabolic acidosis
–> reduced glom filtration; risk of fluid overload
what are the causes of post renal AKI
urinary tract obstruction
- within lumen e.g. renal calculi (stones)
- within wall e.g. benign prostatic hyperplasia
- outside wall e.g. tumour invading ureters
what is important to remember when assessing post renal AKI
- exclude/remove obstruction
- -> rule out urinary retention i.e. catheterise
- -> if catheter present check it is working
- obstruction may still be present above bladder outlet level
- -> urgent USS needed
- treat underlying cause of renal tract obstruction
- prevent/ treat UTI
79 year old women is admitted with severe abdominal pain that’s present for 4 hours.
On examination she is restless and sweating, respiratory rate is 25, oxygen saturation is 96%. pulse is 121, BP is 75/38, temperature is 36.5 and she is alert.
CT scan shows she is bleeding from ruptured abdominal aortic aneurysm and making less than 10ml of urine per hour.
Does she have
a) CKD
b) pre-renal AKI
c) renal AKI
d) post-renal AKI
e) Urinary tract obstruction
b) pre renal AKI
- clinical emergency (rupture aortic aneurysm) caused severe hypotension (shock) and acute loss of kidney function (pre renal AKI)
what are the top causes AKI
- pre renal AKI
- ATN
- post renal AKI (UT obstruction)
- AKI in patients w/ CKD
what can kill Px w/ Aki
- pulmonary oedema (–>resp failure) as a result of fluid overload
- hyperkalaemia
- assc. metabolic acidosis
what to do if kidneys fail
- careful fluid balance to restore effective circulating blood volume
- avoid unnecessary drugs and radio contrast
- treat life threatening hyperkalaemia safely
- seek senior help
what AKI Px is dialysis mostly used w/
ATN
what history would you ask about in suspected AKI
- prior CKD
- fluid losses
- thirst
- nephrotoxins
what examination would you do in suspected in suspected AKI
- pulse
- BP
- O2 sats
- urine output
what investigations would you do in suspected AKI
- urine dipstick
- U&E
- ABG
- ECG
- CXR
- ultrasound
