1
Q
70-year-old Mr Steve Dulles presents
with small bowel obstruction. Initially
treated with “drip & suck”. Did not settle
and had an emergency operation in
which some of the small bowel was
resected.
Post-op he had been making good
progress but the team now notice:
* Low BP
* Postural drop with symptoms
* Reduced urine output
Investigations are shown on the image. What do you think is happening?
A
low pH -> acidosis
low pH with low Co2 -> respiratory compensation
bicarb low = metabolic acidosis
- sepsis secondary to post operative infection
- AKI due to sepsis
- ARD secondary to atelectasis
- HAP
2
Q
AKI may be defined as any one of the following:
(what are they)
A
- increase in serum creatinine by 26.5 umol/l within 48 hours
- increase in serum creatinine to >1.5 times baseline, known or presumed to have occurred within the prior 7 days
- urine output <0.5 ml/kg/h for 6 hours
3
Q
List some risk factors for AKI.
A
4
Q
What are some causes of pre-renal AKI?
A
HYPOPERFUSION OF THE KIDNEYS
- hypovolaemia : haemorrhage, GI losses, hypoproteinaemia, burns, polyuria
- hypotension: sepsis, haemorrhage, GI losses, heart failure
- hypoxia: any cause, ischaemia, aortic aneurysm, clamping of aorta
5
Q
List the types of intrinsic AKI and what you would get with each.
A
6
Q
AKI can be divided into 3 major categories. What are they and what causes them?
A
- PRE-RENAL
- due to poor blood flow to the kidneys - INTRINSIC
- due to direct damage to the kidney itself - POST-RENAL
- due to obstruction to urine flow
7
Q
- What occurs in Acute Tubular Necrosis?
- What occurs in Acute Interstitial Nephritis?
- What occurs in Glomerulonephritis?
- What occurs in Vascular causes?
A
- most COMMON cause of intrinsic AKI
- tubular epithelial cells die due to ischaemia (shock, hypotension, sepsis), nephrotoxins, myeloma light chains, myoglobin/hB (rhabdomyolosis) - INFLAMMATION OF THE TISSUE BETWEEN TUBULES
- pyelonephritis (infection)
- nephrotoxic drugs (penicillins, NSAIDs, PPIs)
- autoimmune disease (SLE) - DAMAGE TO GLOMERULA CAPILLARIES
- primary glomerulonephritis (IgA nephropathy, post-strep GN)
- systemic diseases - AFFECT RENAL BLOOD VESSELS
- vasculitis
- malignant hypertension
- renal vein thrombosis
8
Q
There are 3 categories of AKI. What causes each category?
A
9
Q
What can cause post renal AKI? List 5 things.
A
Luminal (inside the tube i.e the urinary tract - ureter, bladder or urethra)
- renal stones
- blood clots
Mural (in the wall of the tube - when the wall of the ureter, bladder or urethra becomes thickened, scarred or invaded)
- strictures e.g infection, trauma or after procedures like TURP
- tumours e.g transitional cell carcinoma
Extrinsic (outside the tube - when something compresses the urinary tract from outside and narrows it)
- BPH
- pregnancy
- cancer
10
Q
How would you conduct the history and examinations for someone presenting with a type of AKI?
A
11
Q
How would you establish whether the patient was hypovolaemic or in renal failure?
A
HIGH urine osmolality -> hypovolaemic
- high urine osmolality = ADH causes water reabsorption to conserve volume
- low urine sodium = aldosterone causes Na+ reabsorption
- oliguria = kidneys trying to hold on to fluid
(kidneys still functioning and trying to reabsorb water but under perfused)
LOW urine osmolality -> renal failure
- low urine osmolality = tubules cant concentrate urine and water lost inappropriately
- high urine sodium = cant reabsorb sodium
- urine volume may still be low
(kidneys injured and failing)
12
Q
List how you would manage AKI.
A
if septic -> ABX within hour
13
Q
What stage of AKI would the following creatinine levels indicate:
A
14
Q
What would the serum creatinine be for AKI stage 1, 2 and 3?
A
15
Q
What are the indications for renal replacement therapy? List all 5 of them.
A
16
Q
What is this patient’s ECF volume status? Explain your answer.
A
hypovolaemic
- poor oral intake (not eating would limit sodium ion intake)
- postural drop in BP
17
Q
Describe the abnormalities in this patient’s blood.
Would you suspect pre-renal disease in this case? Explain your reasoning, and other potential differential causes of AKI with reference to the patient’s symptoms and test results.
A
- neutrophilia
- hyperkalaemia
- low HCO3-
- elevated glucose
- elevated urea
- elevated creatinine
= filtration or tubular issue? - yes pre-renal AKI is a possibility because of the patient’s hypovolaemia and we could consider filtration and tubular problems
HOWEVER - most likely to be intrinsic kidney damage due to muddy brown urine which indicates blood and protein - possible acute nephritis - not post-renal because patient has passed 200ml of urine in 12 hours - no obstruction, fever and loin pain could be indicative of infection
18
Q
What suggest intrinsic AKI as opposed to pre-renal?
A
URINE Na+ = TOO HIGH FOR SIMPLE PRE-RENAL AKI - KIDNEYS CANNOT CONSERVE SODIUM AT ALL
blood and protein in urine will give muddy brown cast = acute tubular necrosis
19
Q
What could be contributing to this patient’s hyperkalaemia?
A
DEHYDRATION + AKI = poor kidney excretion of K+
- kidneys normally excrete potassium but in AKI they can’t so K+ builds up
MET ACIDOSIS SHIFT K+ OUT OF CELLS
- H+ moves into the cells to buffer acidosis
- K+ moves out into blood to keep electrical balance
H+/K+ EXCHANGE VIA H+/K+ ATPase
- moves H+ in and K+ leaves cell = worsens hyperkalaemia
ACE inhibitor (RAMIPRIL)
- inhibits aldosterone -> less K+ secreted
20
Q
In a hospital environment, what are the primary causes of AKI?
A
- fluid depletion
- sepsis
- drug toxicity
21
Q
- What is your immediate management?
- What do you need to monitor?
- What management will you need to follow if immediate steps do not improve his condition?
A
- correct volume, fluid resuscitation -> IVF, consider possible sepsis and need for appropriate abx, STOP METFORMIN, consider appropriateness for ACE inhibitors
- ions, fluid input, urine output, glucose, BP, close IP/OP monitoring, electrolytes, catheterise
- if no improvement, patient may require dialysis
22
Q
What are the 3 most likely causes for the changes she has noticed in her urine?
A
- UTI
- acute nephritis
- ATN
(low volume and dark colour of urine)
23
Q
The most important immediate test is a urine dipstick. What would you expect it to show?
What would be a hallmark of glomerulonephritis?
A
blood and protein
- exclude urine infection
- find out if patient has nephritis: would see RBCs in urine - red cell cast
red cell casts = hallmark of glomerulonephritis
24
Q
Assuming infection has been excluded from the investigations, which immune diseases would you consider?
A
- systemic vasculitis
- lupus nephritis (SLE) = however lupus causes a butterfly rash not ulcerated purpura
25
The GP is concerned about Mr Zayn's back pain. What features in the history and examination are worrying?
Why did the GP dip the urine?
back pain itself (red flag) - age >50, gradual onset of symptoms, waking him up, localised tenderness
possible underlying malignancy and secondary in spine - symptoms of likely hypercalcaemia (thirsty, passes urine more often and more constipated than usual), tired and pale
diabetes causes polyuria, polydipsia and tiredness but does not cause the other symptoms - those are classic of MYELOMA OR ANOTHER MALIGNANCY -> HYPERCALCAEMIA AND ANAEMIA
EXCLUDE GLUCOSURIA BECAUSE:
- if present you want to know if its diabetes or renal tubular damage
- if absent it rules out diabetes
26
What do the blood tests show? Give possible explanations for each results.
Why is the calcium given as 'corrected calcium' and why may 'corrected calcium' be more relevant in a biological or medical context?
hB = low
MCV = low -> microcytic (small RBCs)
MCH = low -> hypochromic (pale RBCs)
microcytic hypochromic anaemia -> could be iron deficiency or anaemia of chronic disease
low WBC and platelets (+anaemia) = bone marrow problem
raised ESR = inflammation
raised calcium = primary hyperparathyroidism, cancer, drugs that raise calcium, CKD
CORRECTED CALCIUM
- calcium exists in your blood in two forms: bound to proteins (mainly albumin) = inactive AND free (ionised Ca2+) = active and biologically useful
- if someone has low albumin - less calcium is bound so measured calcium will look low even though the active calcium may be normal
- to fix this, labs use a formula to 'correct' for the albumin level giving a better idea of the true (free, active) calcium
27
In regards to PTH, answer the following:
1. How is it made and what is it triggered by?
2. What effect does it have on which organs?
3. What effect does it have on overall blood levels?
1. parathyroid glands
2. intestine = indirectly increases Ca and phosphate absorption
kidneys = reduce calcium excretion, increase phosphate excretion, increased activation of Vit D
bone = increased bone resorption -> release Ca and phosphate in blood
3. increases blood Ca2+ level, decreases phosphate because it makes the kidneys excrete it
28
In regards to Vit D, answer the following:
1. How is it made and what is it triggered by?
2. What effect does it have on which organs?
3. What effect does it have on overall blood levels?
1. from diet/skin -> activated in liver and kidneys, triggered by sunlight, PTH which stimulates final activation in kidney
2. intestine = directly increase Ca2+ and phosphate absorption
kidney = reduces calcium excretion, reduces phosphate excretion
bone = increase bone resorption and new bone formation
3. increases levels of Ca2+ and phosphate
29
Describe the management for raised calcium.
IV saline to correct dehydration and promote urinary excretion of calcium
monitor or replace K+ and Mg2+ as these will be lost in the urine along with Ca2+
IV biphosphonates - reduce bone resorption and GIT absorption
30
Mr. Steven Zayn is a 65-year-old man. He presents to his GP with back pain which has been gradually getter worse over several weeks. The pain now wakes him from sleep.
He has no history of trauma. He says he is tired, thirsty, passes urine more often and is more constipated than usual. On examination, Mr Zayn looks pale, has dry mucous membranes and loss of skin turgor. He has localised tenderness over his lumbar spine. The urine dipstick is negative.
Which class of diuretics would you stop and why?
thiazides - they decrease the urinary excretion of calcium
31
Mr. Steven Zayn is a 65-year-old man. He presents to his GP with back pain which has been gradually getter worse over several weeks. The pain now wakes him from sleep.
He has no history of trauma. He says he is tired, thirsty, passes urine more often and is more constipated than usual. On examination, Mr Zayn looks pale, has dry mucous membranes and loss of skin turgor. He has localised tenderness over his lumbar spine. The urine dipstick
is negative.
He has an X-ray of his lumbar spine. Describe the abnormality and explain the possible causes of this abnormality.
(he has high calcium)
wedge compression fracture
- osteoporosis
- underlying malignancy
32
Mr Zayn is seen by the haematologist. His calcium is corrected, and he is allowed home.
Three months later, his blood tests are as follows:
- Urea 35 mmol/L (2.5—8.0 mmol/L)
- Creatinine 248 µmol/L (60—130 µmol/L)
What are possible causes for Mr Zayn's AKI? How would you try and exclude these causes?
ATN - sepsis
history and clinical exam looking for hypovolaemia/vasodilation (sepsis)
33
Why is it important to search for previous blood results?
At what stage of AKI is Mr Zayn?
to compare past and current results and see whether there has been any changes and if there has been changes - what extent of those changes may have been seen
248/100 = 2.48 = AKI stage 2
34
What is the most likely investigation to be undertake to determine the acid-base problem?
a) metabolic acidosis
b) ABG
35
What is AKI?
acute deterioration in renal function over a few hours/day
36
AKI shows as a rapid increase in what?
AKI shows as a decrease in what?
rapid increase in urea and creatinine
decrease in GFR and urine output
37
Why do you get an increase in urea and creatinine in AKI?
AKI: sudden drop in kidney function, meaning kidneys are not filtering blood properly
- urea (from protein metabolism) and creatinine (from muscle breakdown) are normally filtered out by the glomeruli and excreted in urine
- when GFR drops they accumulate in the blood because they are not being filtered efficiently
38
Why do you get reduced GFR and urine output in AKI?
glomeruli filters blood to form urine
in AKI, something causes:
- low blood flow to glomeruli (pre-renal)
- or damage to glomerular/tubular structure (intrinsic cause)
- or back pressure from blockage (post-renal)
= less blood is filtered per minute = drop in GFR
LOW GFR = LOW FILTRATION = KIDNEYS NOT CLEARING WASTE
39
What are risk factors for AKI?
- polypharmacy
- elderly
- CKD
- renal stones
- BPH
- infection/sepsis
- multiple co-morbities i.e diabetes, HF, liver cirrhosis
40
What causes pre-renal AKI?
List 4 factors which come under pre-renal AKI and one example which could cause each.
decreased blood flow to the kidneys, reduced perfusion and reduced GFR - kidneys themselves are fine they're just not getting enough blood
- hypovolaemia e.g bleeding, dehydration
- decreased CO e.g CHF
- decreased effective circulating volume e.g liver failure
- impaired renal autoregulation e.g drugs like NSAIDs, ACE inhibitors
41
What causes intrinsic AKI?
List 4 factors which come under this and give examples for each.
direct injury to the kidney tissues - glomeruli, tubules or vessels
- acute glomerulonephritis
- tubular damage e.g ischaemia, sepsis, nephrotoxics
- vascular damage - vasculitis, malignant hypertension, TTP/HUS
42
What causes post-renal AKI?
List two examples.
obstruction of urine outflow which leads to back pressure and a reduced GFR
- bilateral ureteric obstruction e.g stones, tumours
- bladder outlet obstruction e.g BPH, prostate cancer
43
Hypoperfusion of the kidneys will lead to what type of AKI?
List some examples on how the kidneys might suffer hypoperfusion.
pre-renal AKI
- hypovolaemia: haemorrhage, GI losses, burns, polyuria, hypoproteinaemia
- hypotension: sepsis, haemorrhage, heart failure
- hypoxia: ischaemia
44
What are the four main anatomical compartments where intrinsic AKI can occur?
tubular (85%)
interstitial (10%)
glomerular (<5%)
vascular (<5%)
45
Which compartment is most commonly affected in intrinsic AKI?
tubules (tubular compartment)
46
What is the most common type of tubular intrinsic AKI?
List four causes of this.
acute tubular necrosis (ATN)
- ischaemia (shock, sepsis)
- nephrotoxic drugs (aminoglycosides, contrast)
- myeloma
- myoglobinuria (rhabdomyolysis)
- heavy metals
47
How can myeloma or heavy metals cause tubular injury?
they release toxic substances that directly damage tubular epithelial cells
48
What is acute interstitial nephritis (AIN)?
Name 3 things that can cause this.
inflammation of the kidney’s interstitial tissue (the space between tubules)
- nephrotoxic drugs (NSAIDs, certain abx)
- autoimmune (SLE)
- pyelonephritis
49
Which auto-immune disease can cause interstitial nephritis?
systemic lupus erythmatosus (SLE)
50
What cancer-related cause can lead to interstitial AKI?
tumour lysis syndrome, where uric acid crystals deposit in the kidney
51
What are the two main glomerular causes of intrinsic AKI?
glomerulonephritis
haemolytic uraemic syndrome
52
How does Haemolytic Uraemic Syndrome (HUS) cause intrinsic AKI?
microthrombi form in renal capillaries, damaging the glomerular endothelium and reducing GFR
53
List 3 vascular causes of intrinsic AKI and explain why they each cause AKI.
vasculitis - immune-mediated inflammation damages small renal blood vessels and impairs perfusion
malignant hypertension - extreme BP damages renal arterioles and glomeruli, leading to ischaemia and necrosis
renal vein thrombosis - blocks venous outflow, leads to increased renal venous pressure and decreased glomerular filtration - renal congestion + ischaemia -> tubular injury -> AKI
54
What gene is often associated with RCC?
VHL
RCC, particularly the clear cell subtype - is strongly associated with deletion, nonsense, and frameshift mutations involving the von Hippel-Lindau (VHL) gene at chromosome 3p
55
What AKIs are caused by each of the following:
a) ischaemia
b) auto-immune (SLE)
c) shock
d) heavy metals
e) myeloma
f) HUS
g) nephrotoxics
h) pyelonephritis
a) ATN
b) AIN
c) ATN
d) ATN
e) ATN
f) glomerular
g) ATN / AIN
h) AIN
56
What is the mechanism of injury in nephrotic syndromes?
What is the mechanism of injury in nephritic syndromes?
nephrotic
- injury to podocytes
- changed architecture: scarring, deposition of matrix or other
nephritic
- inflammation
- reactive cell proliferation
- crescent formation
57
1. What urinary diseases are nephrotic and what is their main issue?
2. What urinary diseases are nephritic and what is their main issue?
1. NEPHROTIC
- minimal change disease, FSGS, membranous glomerulopathy, diabetic nephropathy
- issue: damage to podocytes -> leaky filtration barrier = MASSIVE PROTEINURIA
- features: proteinuria, hypoalbuminaemia, hyperlipidaemia
2. NEPHRITIC
- IgA nephropathy, post-strep GN, small cell vasculitis, anti-GBM disease
- issue: inflammation of glomeruli -> breaks in GBM -> HAEMATURIA
- typical features: haematuria, hypertension, reduced GFR, mild/mod proteinuria
58
What is SLE?
What is IgA Nephropathy?
SLE: auto-immune disease where your immune system attacks your own tissues, including the kidneys
- immune complexes get deposited in the glomeruli, triggering an inflammation and damage
- CAN RANGE FROM NEPHROTIC TO NEPHRITIC DEPENDING ON HOW SEVERE IT IS
IgA Nephropathy: excess or abnormal IgA antibodies deposit in the mesangium (central part of the glomerulus) = inflammation
59
What happens to tubular epithelial cells in ATN?
trigger: ischaemia or nephrotoxic injury
INITIATION PHASE
tubular epithelial cells suffer from oxygen deprivation:
- loss of brush border
- loss of cell polarity
- reduced reabsorption -> tubular fluid builds up -> reduced GFR
INJURY/EXTENSION PHASE
- necrosis and apoptosis of tubular cells
- sloughing of dead cells into tubular lumen -> cast and obstruction
- filtrate backs up, pressure increases, GFR drops even more
RECOVERY PHASE
- surviving cells dedifferentiate and proliferate
- they migrate and replace dead cells
- RE-ESTABLISHMENT OF POLARITY AND BRUSH BORDER RESTORES NORMAL FUNCTION
- gradual return of GFR and urine output
60
What happens to the Na+/K+ ATPase pump in cells in ATN?
cells lose their polarity and the Na+/K+ pump moves to the wrong (luminal) side
(from the basolateral membrane which is where they are supposed to be)
61
What happens to adhesion molecules in cells in ATN?
normally they help tubular cells stick to the basement membrane and to each other which maintains tubular structure but in ATN:
- adhesion molecules are lost or disrupted
- cells detach and slough off in the tubular lumen which causes obstruction by dead cells and casts = contributes to back-leak of filtrate and worsens kidney injury
62
What happens to the tubular epithelial cells during ATN?
- they lose their brush border
- lose cell polarity
- undergo necrosis/apoptosis
- slough off in the lumen causing obstruction
63
What does "loss of cell polarity" mean"
cell loses its distinction between apical and basolateral sides — its internal organization and transport direction are disrupted
64
What are the phases of ATN?
(of cellular damage)
initiation
injury (extension)
recovery
65
List 5 nephrotoxins.
- certain meds: aminoglycosides e.g gentamicin, amikacin + diuretics
- bacterial endotoxins e.g E.coli
- IV iodinated contrast media
- heavy metals such as cadmjum
- tumour lysis syndrome (cancer cells die rapidly -> hyperuriceamia)
66
List 6 symptoms/signs of AKI.
- features of underlying cause
- non-specific nausea and lethargy
- decreased urine output
- haematuria
- fluid overload (oedema, pulm oedema = SOB)
- electrolyte abnormalities
- acid base disturbances
- arrhythmias
- seizures, confusion, altered LOC
Med Term 3
flashcards
Decks in class (44)
# Cards
-
HPD 154
-
HPD 272
-
HPD 343
-
HDP 4 and 5101
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HPD 6 and 7100
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HDP 8 and 970
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HSD 10 and 1184
-
HSD 11.265
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Urinary System 1140
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Urinary 2112
-
Urinary 368
-
Urinary 463
-
Urinary 551
-
Urinary 697
-
Urinary 789
-
Urinary 8137
-
Urinary 963
-
Urinary 1066
-
CVS 1129
-
CVS 294
-
CVS 390
-
CVS 465
-
CVS 589
-
CVS 6141
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CVS 7112
-
CVS 8106
-
CVS 986
-
CVS 1063
-
CVS 1181
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Respiratory 1132
-
Respiratory 2135
-
Respiratory 3115
-
Respiratory 480
-
Respiratory 5156
-
Respiratory 672
-
Respiratory 771
-
Respiratory 876
-
Respiratory 9112
-
Respiratory 10103
-
Respiratory 11117
-
OSCE practise15
-
ECGs117
-
PASSMED10
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TERM 3 REVISION737
