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Cardiff MRCS OSCE Course www.doctorsacademy.
org
MRCS Course
Renal physiology lecture
Dr Gareth Scholey MA FRCP DICM FFICM
Consultant in Intensive Care
University Hospital of Wales
Cardiff MRCS OSCE Course www.doctorsacademy.org
Aim of Lecture
Basic What is renal Causes and

physiology failure treatments
• Principles • Case • Diseases

• answer most examples affecting
questions • Concepts nephron &
help you as global
doctor disease.
MRCS April 2014 2

Basic Anatomy
Nephron basic unit of kidney
1.3x 106 in each person.

25% cardiac output = 1.2L /min Functional unit of kidney
MRCS April 2014 3

Basics
• 25% cardiac output • Oxygen consumption

• Renal blood flow 1.2L/min high
• Renal plasma flow – • A-V difference low
600ml/min Due to high amount blood
• Cortex – 500ml/100g/min flow
• Medulla 100ml/100g/min
• Metabolism
• Active transport
• Maintenance GFR
MRCS April 2014 4

Question: Which of these people seen in

Out-patients have renal failure & why?
• A: 80 yr old lady, awaiting hip surgery. Well, Urea 8,
Creatinine 90. Blood pressure 145/80.
• B: 56yr man following ERCP for pancreatitis due to gall
stones. Urine dipstick –NAD, Na 140, K 5, Urea 11, Cr 186.
(at discharge Ur 20, Cr 210).
• C: new referral urology clinic 36yr lady with recurrent renal
stones. Dipstick blood 4+, nil else, creatinine 150, urea 18.
• D: 75yr old post AAA repair, renal function pre-op ‘normal’, in
clinic Creatinine 380, urea 15.
Answer: They all could. Results are all

context specific. MRCS April 2014 5
What is renal failure? Change in

measured GFR
• Kidney stops doing its job probably
– Make urine
 acid/metabolic by-product removal
 electrolyte homeostasis
 water balance
 Endocrine function
• Acutely or slowly (Chronic).

• Defined as change in measured surrogate for ‘GFR’.
MRCS April 2014 6

Capillary – blood
squeezes fluid out
through seive.
Glomerular Filtration rate
Collected in
‘funnel’
Reabsorb
99% this
Urine in
bladder Glomerular
filtration Rate
Men 125ml/min
Women 100ml/min
MRCS April 2014 7

Nephron
Glomerular filtrate GFR 125ml/min. 180L per day
(capillary)
Resembles plasma Electrolyte concentrations similar
Volume reduced
Composition altered
Urine volume 2
Tubular contents – renal pelvis - L/day
urine Composition
differs
MRCS April 2014 8

Table of urine concentration
Urine Plasma
mg/dL mg/dL
Glucose 0 100
Sodium 90 150
Urea 900 15
creatinine 150 (13200) 1 (88.8umol/L
MRCS April 2014 9

A: 80 yr old lady, awaiting hip surgery. Urea 8,

Creatinine 90. Blood pressure 145/80.
How could this be renal failure?
What is creatinine?
How do we assess renal function?
MRCS April 2014 10

How GFR varies with Creatinine

Muscle mass, age, race
Gender, diet and lab test.
Normal range – 50% loss
400 GFR.
B
Creatinine
80
10 50 100
GFR ml/min
MRCS April 2014 11

Estimating renal function
• Blood test
• Urinary dipstick
• Radiology (functional vs static)
• Direct measures (EDTA, inulin).
• Formulae (Crcl, eGFR (MDRD), CG formula).
MRCS April 2014 12

D: 75yr old post AAA repair, renal

function pre-op ‘normal’, in clinic
Creatinine 380, urea 15.
An acute rise in his creatinine – likely represents renal failure.
Why could he have a kidney injury?
MRCS April 2014 13

Ischaemic ATN
CKD, Atherosclerosis,
DM, malignancy,
poor nutrition
Patient factors
SURGERY
Preop fluid balance

Haemodynamic changes
fluid loss AAA
Although RBF falls tolerated Obstructive jaundice
Valve surgery
sepsis
Endotoxinaemia,
SBP low, Renal vasoconstriction,
inflammatory cells.
MRCS April 2014 14

• B: Post-admission review of 56yr man following ERCP for

pancreatitis due to gall stones. Urine dipstick –NAD, Na 140,
K 5, Urea 11, Cr 186. (at discharge Ur 20, Cr 210).
• C: 36yr lady with recurrent renal stones. Dipstick blood 4+, nil
else, creatinine 150, urea 18.
How do we define acute & chronic kidney injury?
What is eGFR?
Is it relevant?
MRCS April 2014 15

Definitions of Acute Renal Failure
RIFLE Classification/staging system for acute

Uchino s et al Critical Care Medicine 2006 Volume 34 No.7 kidney injurya AKIN
Mehta et al. Critical Care 2007 11:R31
Serum Cr > 0.3 mg/dl Less than 0.5
1 (≥ 26.4 μmol/l) ml/kg per hour for
or increase 150% to more than 6 hours
200% (1.5- to 2-
fold) from baseline
Increase in serum Less than 0.5

2 creatinine to more ml/kg per hour for
than 200% to 300% more than 12
(> 2- to 3-fold) from hours
baseline
Increase in serum Less than 0.3

3 creatinine to more ml/kg per hour for
than 300% (> 3- 24 hours or anuria
fold) from baseline for 12 hours
(or serum creatinine
of more than or
equal to 4.0 mg/dl
[≥ 354 μmol/l] with
an acute increase of
at least 0.5 mg/dl
[44 μmol/l])
MRCS April 2014 16

KDIGO definition of AKI.
• Combination of RIFLE / AKIN
• Absolute rise in Cr of 0.3mg/dL (26.4 umol/L) in 48hrs OR

• >50% baseline Cr within seven days.
• Use urine output results as well
• No use of eGFR.
MRCS April 2014 17

Chronic kidney disease eGFR
Stage GFR* Description

1 90+ Normal Function, other
sign of kidney disease-
protein, structural,
genetic
2 60-89 Mild
3A 45-59 Moderate
3B 30-44 A B categories reflect
different progression
4 15-29 Severely reduced
5 <15 or on dialysis ESKD
MRCS April 2014 18

Mortality of AKI
• 1996-2005
• 91,254
• AKI 4754 (5.2%)
• Hospital mortality 42.7% vs 13.4%
• Increase AKI 2.8%/yr
• Decrease AKI mortality 3.4% / yr
• No change in other groups
Bagshaw 2007 Crit Care 11(3) R68

MRCS April 2014 19
Nephron Structure & Disease
Scenarios and questions highlight how the nephron works
Part of syllabus : know function of nephron and diseases.
MRCS April 2014 20

Case Scenario 1
• 76 year old man is admitted under ENT surgeons for recurrent

sinusitis. He has a history of non specific symptoms of
headache, malaise, weight loss, recurrent nasal infections,
joint aches and occasional haemoptysis (which is felt to be
related to nose bleeds). He has become very short of breath
on the ward.
• Investigations Hb 7.6, WCC 4.3, Plts 130, Na 145, K5.9, Ur
23, Cr 310 (previous blood 2 months ago normal), ESR 111,
urine blood 4+, protein 3+.
MRCS April 2014 21

Alveolar Haemorrhage
What is a possible diagnosis?

Pulmonary Renal syndromes
e.g WG
What does his x-ray show?
Where is the pathology in his

kidney’s?
MRCS April 2014 22

Nephron Structure
• Glomerulus
• Bowman’s capsule
• Proximal tubule
• Loop of henle
• Distal tubule
• Collecting ducts
(cortical & medullary)
MRCS April 2014 23

Glomerulus
 Capillary bed INTRINSIC disease

 Three layers between  Thin basement membrane,
blood and tubule Alport’s
Capillary endothelium  Nephrotic – minimal change
Basal lamina  IgA nephropathy
Epithelium (specialized) –  Diabetes
podocytes form small
pores @ 4nm. ‘Active urinary sediment’
Mesangial cells between Blood and protein
basal lamina &
endothelium.
Limit – size and charge.
MRCS April 2014 24

Case scenario 2
45 year referred to urology clinic for investigations into

Recurrent UTIs. History of progressive tiredness, lethargy and
weight loss.
She reports symptoms she thinks are recurrent urine infections.
She is constantly thirsty all the time but probably because she
keeps going to bathroom.
What is a simple & common non- surgical diagnosis for these symptoms?
What simple bedside test could you do to prove you are right?
What has this to do with kidney function? Diabetes

Urine dipstick
MRCS April 2014 25
Nephron Structure
• Glomerulus
• Proximal tubule
• Loop of henle
• Distal tubule
MRCS April 2014 26

Proximal tubule
• Reabsorb sodium
• Water
• Bicarbonate
• Chloride
• Glucose
• Amino-acids
• Protein
• Phosphate
MRCS April 2014 27

Glucose
• Symport with sodium

• All reabsorbed in PT.
• Tubular maximum concept
MRCS April 2014 28

Case Scenario 3
7 am bleep
‘Quick – Mr AB is really SOB, he was OK a minute ago but now
has sats of 89% and cannot talk. He sounds really bubbly’
74yr smoker, had a TURP the previous day. He had received 3L
fluids overnight due to low blood pressure.
• CXR been ordered by ward staff.
MRCS April 2014 29

CXR
What does the

CXR show?
What is the likely

cause?
How do you treat?
Where in the
kidney does your
drug(s) work?
MRCS April 2014 30

Nephron Structure
• Glomerulus
• Proximal tubule
• Loop of henle
• Distal tubule
MRCS April 2014 31

Loop of Henle
Countercurrent multiplier
Interstitial hypertonicity of
medulla.
•Ability to concentrate urine
•40-1200mosmol/kg water
•Thick and thin walls.

•Thick wall impermeable water
•Actively extrudes sodium,
potassium, chloride.
•15% nephrons contribute to
majority of gradient
MRCS April 2014 32

Loop diuretics
• TAL Cell
Loop of Henle.
Tubule – filtered and
excreted as an acid.
Bind Na/2Cl/K transporter
TAL.
Diminish cortico medullary
gradient.
Increase [Na] in lumen.
More Na to DCT. Reduce
ability to make dilute urine.
High doses 30% filtered Na
excreted
MRCS April 2014 33

Thiazides
Organic acids
Lumen same way
Early DT Na/Cl
cotransporter.
More Na reaches
Na/K transport
downstream.
Less potent
10% filtered load
excreted Na and
water.
MRCS April 2014 34

Spironolactone
• Aldosterone antagonists
• Principal cells of collecting duct
• Opposite to aldosterone {Na absorption, H/K secretion} – Na
excretion retention of K
• Little diuretic ability.
MRCS April 2014 35

Summary slide Diuretics loop,

thiazides increase
urine flow.
Glomerular
disease
TBM,
goodpasture
GN
Diabetes
insipidus
DM,
congenital,
ATN
AIN, CIN
Active urinary sediment – glomerular

MRCS April 2014 36
disease
Clinical Scenarios
Autoregulation
Renal response to Renin, Angiotensin, Aldosterone.
Causes of Renal failure
Treatments.
MRCS April 2014 37

Case scenario 4: Autoregulation
65yrs Mr Fortune, diabetic

Admitted for his infra renal
aneurysm repair.
Meds: Ramipril,
Bumetanide
Ibuprofen prn
MRCS April 2014 38

Anaesthetic room
With respect to his

kidneys :
How does his kidneys

protect themselves
against this sudden
drop in pressure?
Induction
Propofol/fentanyl
MRCS April 2014 39

Autoregulation
• Renal blood flow

preserved to maintain
a relatively constant
filtration rate.
• Not always same
• Flow independent of
pressure.
Denervated kidney
maintain perfusion
Isolate kidney same.
MRCS April 2014 40

Feed-back in op BP falls
Perfusion
pressure falls AG II
vasoconstriction
GFR falls
EFF> AFF
Less filtrate
Transglomerular
Less Na reaches pressure rises
JGA GFR normal
MD renin to help
increase ECV
MRCS April 2014 41

Juxtaglomerular apparatus
DCT passes next to

afferent & efferent
arteriole.
• DCT modified – MD
• Afferent artery – renin

secreting cells.
MRCS April 2014 42

3 stimuli to renin release

Renin
a) Direct sympathetic stimulation (low
ECV, Low CO, low Na)
Angiotensinogen b) Reduced pressure in afferent
arteriole . (baroreceptor)
c) Reduced delivery [Na] to DCT and
Angiotensin I sensed by MD.
Angiotensin II
Adrenal gland – z glomerulosa

Release aldosterone
Vasoconstrictor esp. intrarenally
Increases Na resorption in PCT

Acts on Na/H pump
aldosterone DCT increases Na uptake
Stimulates ADH
Thirst
Negative feed back on renin.
MRCS April 2014 43
Case scenario 5
Mrs EY 70yr old lady fell at home. Significant pain in her right
groin but tried to manage. She found it increasingly difficult to
mobilise and took to her bed. She took pain killers incl.
NSAIDS & paracetamol. After three days she saw her GP who
sent her to hospital. PMH Hypertension for which she took
bendrofluazide.
Wt 80 kg. Hr 99, BP 110/65 JVP not visible, Thirsty++
Day 3 Urea 66.2, Cr 502, Urine output – 10mls / hr for 6 hrs.
(Day 1 Ur 36.6, Cr 136, K 5.4)

MRCS April 2014 44
• What is the cause of her

AKI?
• How do you define causes

of AKI?
• How should we treat Mrs

EY?
• What nephrotoxic drugs are

there?
MRCS April 2014 45

Answers
• What is the cause of her AKI?

• Hypovolaemia &
nephrotoxic drugs
• How do you define causes of AKI?
• See slide
• How should we treat Mrs EY?
Fluids, close observation
regular bloods
• NSAIDS,
Aminoglycosides,
ACE,ARB, BP drugs
&diuretics(context)
MRCS April 2014 46

Effective circulating volume: low

Physiology
• Fluid deplete – many losses
• Perfusion pressure low.
• Renin, AG, Aldosterone.
• Retain sodium DCT, retain water
• ADH – posterior pituitary
• Needs some fluid – prescribed.

• Eat & drink if possible.
• Hold anti-hypertensives.
• Avoid NSAIDS.
MRCS April 2014 47

Hypovolaemia /
Pre Renal Hypoperfusion
•Hypovolaemia Low volume status

‘hypoperfusion’ Poor ‘pump’ function
Sepsis, bleeding, Sepsis
dehydration.
Cardiac impairment
Renal
• ATN :Acute tubular Necrosis ATN

• GN, Vasculitis
• Interstitial nephritis,
• AntiGBM,
• Cryoglobulins, (HUS/TTP,
myeloma),
• Acute cortical necrosis.
Post Renal
•Prostate,
•stones, tumours, LN
• blocked catheter. MRCS April 2014 48
Case Scenario 6:
• 63 yr old male previous
breast cancer, presents
SOB, blood pressure 80 /
50; new acute kidney
injury Cr 400 & urea 28;
been SOB for few weeks
• What is diagnosis?
• What is the cause of his
renal failure?
• What is treatment?
MRCS April 2014 49

Pericardial effusion (malignant)
• Poor CO, Perfusion

pressure to kidneys low.
• Renin, AG, aldosterone.
• Retain sodium DCT,
retain water
• ADH – posterior pituitary
• Consequence reduced
GFR, leads to reduced
perfusion to medulla.
MRCS April 2014 50

Case Scenario 7
Mr DS 65 yr old man ex smoker, underwent a procedure

before Xmas (see CT/Xray). He was seen in clinic at end
of December but then re-presented c/o lethargy and
nausea
MRCS April 2014 51

Dec
urea 4, Cr 83 (Pre
procedure.)
End Dec
urea 9, Cr 101
6th Jan
urea 19, Cr 278
What Operation did he have?

What are the possible causes?
What Investigations do you want?
Is there anything you would do before hand?
MRCS April 2014 52
Answers
• Mr DS 65 yr old man ex smoker, underwent a procedure

before Xmas (see CT/Xray). He was seen in clinic at end of
December but then re-presented c/o lethargy and nausea
EVAR for thoraco-abdominal aneurysm.

AKI – Contrast,Injury renal arteries,Stent slipped, Extension, Intercurrent
illness.
Rx: CT scan – contrasted.
Hydration, Bicarbonate.
MRCS April 2014 53

Prevent contrast-induced acute renal

failure
• Hydration most important.

• Normal function no precautions needed.
• GFR < 60ml/min : Volume expansion isotonic fluid. (6-

12hrs pre & post)
• low osmotic dyes
• Sodium bicarbonate
Worse renal function consider N Acetylcysteine 600mg bd

GFR < 15ml/min may consider prophylactic RRT.
MRCS April 2014 54
Case Scenario 8 (A.N.Other hospital)

71 year old lady admitted following a fall.
•T2DM
–Hypertension
–retinopathy
•CKD IV under nephrology – (DM )
–Expectation may need dialysis
–Baseline Creatinine 280.
•Frusemide Doxazosin Bisoprolol
Atorvastatin Insulin Paracetamol
Hb 11g/dL, WCC 12, CRP 187. Plts 380

PT n, APTT n
Na 134, K 6.7, Ur 24, Cr 370
(immediately post op Ur 24, Cr 340, K 6.2)
Oramorph – @ 20mg for pain.
What is the biochemical abnormality?

What investigations are needed?
What treatment would you give?
MRCS April 2014 56

CXR
ECG
ABG (on 2l O2 nc)

pH 7.30
PCO2 3.8 kPa
PO2 11.0 kPa
BE -4.0
Lactate 1.8
MRCS April 2014 57

Managing Hyperkalaemia
How do you manage What happens to our patient?

hyperkalaemia?
• 10mls 10% CaCl –
• 10 iu insulin + 50ml 50% dextrose.
• Calcium gluconate/ chloride • Day 3 K 7.4, Cr 491, pH 7.14. u/o
500mls.
– Further Insulin/ dextrose
• Insulin/dextrose
• Day 4 K 6.8, Cr 471, ur 38
– Insulin dextrose
• Bicarbonate • Day 5 K 7.0, Cr 529, ur 36.9
– Insulin/dex x2 plus salbutamol
• Salbutamol • Day 6 K 7.4, Cr 500, ur 38
– 20 iu Insulin/dex x 3/day
• Calcium resonium – Calcium resonium
• Day 7 K 6.6, Na 117, Cr 441
– BE -12, pH7.2
• Frusemide
– ITU recalled. Renal team recalled
– Transferred UHW – dialysis.
• TREAT CAUSE.
MRCS April 2014 58

What drug should you give immediately ?
A 10ml 10% dextrose iv

B 10iu Insulin in 50ml 50% dextrose
C 10ml 10% Calcium Chloride
D 100 ml 8.4% sodium bicarbonate
HYPERKALAEMIA
(severe)
MRCS April 2014 59

Initiation of dialysis
Classical indications
•Rapidly rising urea and creatinine or uraemic complications
•Hyperkalaemia
•Acidosis Failing medical management
•Diuretic resistant pulmonary oedema

•Oliguria,anuria
Non-renal indications
•Management of fluid balance e.g. cardiac failure
•Correction of electrolyte abnormalities
•Temperature control
•Removal toxins/ mediators/ cytokines
MRCS April 2014 60

Summary
Clinical application of nephron and disease.

Relevance clinically auto regulation.
Hormonal response R-A-A
Surgical case – risks of AKI
Definition AKI
Causes of AKI
Management.
MRCS April 2014 61

Thank you!
MRCS April 2014 62

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Cardiff MRCS OSCE Course www.doctorsacademy.

Basic What is renal Causes and

• Principles • Case • Diseases

MRCS April 2014 2

1.3x 106 in each person.

MRCS April 2014 3

• 25% cardiac output • Oxygen consumption

MRCS April 2014 4

Question: Which of these people seen in

Answer: They all could. Results are all

What is renal failure? Change in

• Acutely or slowly (Chronic).

MRCS April 2014 6

Glomerular Filtration rate

MRCS April 2014 7

Resembles plasma Electrolyte concentrations similar

MRCS April 2014 8

Table of urine concentration

MRCS April 2014 9

A: 80 yr old lady, awaiting hip surgery. Urea 8,

How could this be renal failure?

How do we assess renal function?

MRCS April 2014 10

How GFR varies with Creatinine

MRCS April 2014 11

Estimating renal function

• Radiology (functional vs static)

• Direct measures (EDTA, inulin).

• Formulae (Crcl, eGFR (MDRD), CG formula).

MRCS April 2014 12

D: 75yr old post AAA repair, renal

An acute rise in his creatinine – likely represents renal failure.

Why could he have a kidney injury?

MRCS April 2014 13

Preop fluid balance

MRCS April 2014 14

• B: Post-admission review of 56yr man following ERCP for

How do we define acute & chronic kidney injury?

MRCS April 2014 15

Definitions of Acute Renal Failure

RIFLE Classification/staging system for acute

Increase in serum Less than 0.5

Increase in serum Less than 0.3

MRCS April 2014 16

KDIGO definition of AKI.

• Combination of RIFLE / AKIN

• Absolute rise in Cr of 0.3mg/dL (26.4 umol/L) in 48hrs OR

• Use urine output results as well

MRCS April 2014 17

Chronic kidney disease eGFR

Stage GFR* Description

5 <15 or on dialysis ESKD

MRCS April 2014 18

Bagshaw 2007 Crit Care 11(3) R68

Nephron Structure & Disease

Scenarios and questions highlight how the nephron works

Part of syllabus : know function of nephron and diseases.

MRCS April 2014 20

• 76 year old man is admitted under ENT surgeons for recurrent

MRCS April 2014 21

What is a possible diagnosis?

Where is the pathology in his