Renal anatomy and physiology

1. Renal anatomy and physiology in relation
to anaesthesia & Renal function test
By- Dr.Sathyaprabu.V( 1st yr PGT)
Dept of Anaesthesiology&Critical care
GUIDE- Prof Dr. Nibedita pani
Dept of Anaesthesiology&Critical care
SCB MCH, Cuttack

2. Introduction
• The kidneys are a pair of highly vascular organs located in the
retroperitoneal space against the posterior abdominal wall between
the transverse process of T12-L3 vertebrae.
• They are approx. 12cm long & 150 gram each. The right kidney is
lower than the left kidney due to the position of liver.

3. Blood supply
The renal arteries arise from the lateral aspect of the abdominal aorta
at L2 vertebral level & enters the kidney through the renal hilum.

4. Nephron
• Length of each nephron is 45-65nm
• Each adult kidney contains around 1-1.5 million nephrons

6. Juxtaglomerular apparatus
• Macula densa – specialised cells in the wall of the tubule that
are capable of sensing and responding to the composition of
tubular fluid.
• Afferent arteriole granular cells – specialised cells in the
wall of afferent arterioles that secrete renin.

8. RENAL BLOOD FLOW
• The kidneys receive a total blood flow of 20-25% of the cardiac
output.
• The blood flow is not evenly distributed throughout the kidney
and is not related to the level of metabolic activity.
• The cortex receives 80% of blood flow, which is the least
metabolically active, while only 10-15% goes to the more
metabolically active medulla.
• Cortex blood flow – 500ml/min/100g
• Outer medulla blood flow – 100ml/min/100g
• Inner medulla blood flow – 20ml/min/100g

9. Mechanisms of Urine Formation

10. THE GLOMERULUSAND ITS FUNCTION
The glomerulus essentially acts as a filter, producing an
ultrafiltrate of the plasma from the glomerular capillaries that
enters the Bowman’s space.
Structure of the filter

11. The degree to which solutes are filtered is dependent on two physical
properties:
• Molecular weight
• Less than 7000 Daltons – molecules will be freely filtered
• Greater than 70 000 Daltons – molecules are essentially not filtered at
all
• In between 7000 and 70 000 Daltons - the percentage of a molecule
that is filtered decreases with increasing weight
• Electrical charge
• For any given molecular weight between 7000 and 70 000 Daltons a
lower percentage of negatively charged molecules will be filtered
• This is due to the basement membrane having a negative charge and
therefore repelling negatively charged molecules

12. Glomerular Filtration
Volume of fluid filtered from the glomerular capillaries into
bowman’s capsule per unit time.
 Governed by (and directly proportional to)
• Total surface area available for filtration
• Filtration membrane permeability
• NFP
Normal values - 120 +/- 25 ml/min (male)
95 +/- 20 ml/min (female)
Calculated using inulin or creatinine clearence
filtration fraction  GFR/RPF = 20%

13. REGULATIONOFGLOMERULARBLOODFLOW
GFR is regulated using three mechanisms
1. Renal Autoregulation
2. Neural regulation
3. Hormonal regulation

14. Renal Autoregulation
Goal: maintain constant filtration under variations in
arterial pressure
• Maintains a nearly constant GFR when MAP is in the
range of 80–180 mm Hg
• Two types of renal autoregulation
• Myogenic mechanism
• Tubuloglomerular feedback mechanism, which
senses changes in the juxtaglomerular apparatus.

15. Myogenic Mechanism
 BP  constriction of afferent arterioles
• Helps maintain normal GFR
• Protects glomeruli from damaging high BP
 BP  dilation of afferent arterioles
• Helps maintain normal GFR

16. TubuloglomerularFeedbackMechanism
Flow-dependent mechanism directed by the Macula densa cells.

17. Neural regulation of GFR
• Kidneys are supplied by sympathetic ANS fibres that cause
vasoconstriction of afferent arterioles.
• At rest, sympathetic activity is minimal renal blood vessels are
maximally dilated  renal autoregulation predominates.
• With moderate sympathetic stimulation, both afferent & efferent
arterioles constrict equally  blood flow decreases  decreases GFR
slightly.
• With extreme sympathetic stimulation ( exercise or hemorrhage),
vasoconstriction of afferent arterioles reduces blood flow  reduces
GFR  lowers urine output & permits blood flow to other tissues.

18. Hormonal regulation of GFR
• Renin-Angiotensin Mechanism
• Renal prostaglandins
• Atrial natriuretic peptide (ANP)
• Nitric oxide
• Endothelin

19. Renin-Angiotensin Mechanism

20. Renal prostaglandins
When renal blood flow is compromised.
Afferent arteriole vasodilatation & maintain glomerular blood flow
and GFR.
Atrial natriuretic peptide
ANP is released in response to increased atrial stretch
cause vasodilatation of the afferent arterioles
increase GFR.

21. Tubular reabsorption & Secretion

22. The Proximal Tubule
• Of the Ultrafiltrate formed in Bowman’s capsule 65–75% is
normally reabsorbed in the proximal tubules.
• The first part of the proximal tubule reabsorbs about 100% of
the filtered glucose, lactate, and amino acids.
• The major function of the proximal tubule is Na+ reabsorption.
Sodium is actively transported out of proximal tubular cells at
their capillary side by Na-K-ATPase.
• H+ are extruded into the tubule in exchange for bicarbonate by a
sodium-H+ antiporter system.

23. THICK ASCENDING LOOP OF HENLE
• It reabsorbs about 20% of the filtered sodium, chloride,
potassium, and bicarbonate.
• In thick ascending loop, sodium is actively reabsorbed, but water
remains.
• In this so-called diluting segment of the kidney, tubular fluid
osmolality decreases to less than 150 mOsm/kg.
• An important symporter protein system couples the reabsorption
of sodium, chloride, and potassium across the apical membrane.
• Blockade of this system is the major site of action of loop
diuretics.

24. DISTALTUBULE AND COLLECTINGDUCT
• The proximal segment of the distal tubule is structurally and
functionally similar to the thick ascending limb.
• Sodium reabsorption is mediated by an apical cell membrane NaCl
symporter system, which is the site of action of thiazide diuretics.
The last part of the distal tubule is composed of two types of cells.
• Principal cells reabsorb sodium , water and secrete potassium via
the Na-K-ATPase pump
• Intercalated cells secrete H+ and reabsorb bicarbonate.

25. Urine Concentration And Dilution
Importance:
• When there is excess water osmolarity is reduced, the kidney
can excrete urine with an osmolarity as low as 50 mOsm/liter.
• Conversely, when there is deficiency of water and extracellular
fluid osmolarity is high, the kidney can excrete urine with a
concentration of about 1200 to 1400 mOsm/liter.

28. Renal function test

29. Why test renal function?
 To assess the functional capacity of kidney.
 Severity and progression of the impairment.
 Monitor the safe and effective use of drugs which are
excreted in the urine.
 Monitor response to treatment.
 Early detection of possible renal impairment.

30. When should we assess renal function?
 Older age
 Family history of Chronic Kidney disease (CKD)
 Diabetes Mellitus (DM)
 Hypertension (HTN)
 Autoimmune disease
 Systemic infections
 Urinary tract infections (UTI)
 Nephrolithiasis
 Obstruction to the lower urinary tract
 Drug toxicity

31. Biochemical Tests of Renal Function
• Measurement of GFR
▫ Clearance tests
▫ Plasma creatinine
▫ Urea, uric acid and β2-microglobulin
• Renal tubular function tests
▫ Osmolality measurements
▫ proteinuria
▫ Glycosuria
• Urinalysis
▫ Appearance
▫ Specific gravity
▫ pH
▫ Glucose
▫ Protein
▫ Urinary sediments

32. Glomerular Filtration Rate
• GFR = rate (mL/min) at which substances in plasma are
filtered through the glomerulus.
• Best indicator of overall kidney function
• In the normal adult, this rate is about 120 ml/min; about
180 litres/Day

33. Measurement of GFR
Clearance tests
Plasma creatinine
Urea, uric acid and β2-microglobulin

34. Clearance
Clearance is defined as the volume of plasma cleared of a
substance per unit time.
C = (U x V)/P
▫ C = clearance
▫ U = urinary concentration
▫ V = volume of urine produced/min
▫ P = plasma concentration

35. Markers of GFR
• Ideal characteristics:
Freely filtered at the glomerulus
No tubular secretion or reabsorption
No tubular metabolism
Types of markers
• Exogenous –Inulin, 124I-iothalamate, 48Cr-EDTA
• Endogenous -- Creatinine.

36. Inulin clearance
The Volume of blood from which inulin is cleared or completely
removed in one min is known as the inulin clearance and is
equal to the GFR.
Male-110 to 140 mL/ min/1.73m2
Female- 95 to 125 mL/min/1.73m2
• Gold standard for renal clearance
▫ Freely filtered at glomerulus
▫ No tubular metabolism
▫ No tubular reabsorption or secretion
• Limitations
▫ Expensive, hard to obtain.
▫ Difficult to assay & invasive.

37. Creatinine
1-2% of muscle creatine spontaneously converts to creatinine
daily and released into body fluids at a constant rate.
Since Creatinine is released into body fluids at a constant rate
and its plasma levels is maintained within narrow limits
Creatinine clearance may be measured as an indicator of GFR.
Endogenous creatinine produced is proportional to muscle
Mass the production varies with age and sex.

38. Creatinine Clearanace
Creatinine clearance in adults is normally about of
120 ml/min.
Advantages
▫ Endogenous
▫ Produced at a constant rate per day
▫ Routinely measured
▫ Freely filtered at glomerulus
Disadvantages
▫ 10% is secreted by renal tubules

40. Creatinine Clearance
Plasma creatinine derived from muscle mass which
is related age, weight, sex.
 COCKROFT GAULT EQUATION
eGFR(ml/min/1.73m2) = (140-age) x wt in kg / s.creat x 72
For females, the result is multiplied by 0.85 to obtain the
derived GFR.
 MODIFICATION OF DIET IN RENAL DISEASE
eGFR(ml/min) = 175 x sr. creat(-1.154) x age(-0.203)
For females, the derived eGFR is multiplied by 0.742

41. The Schwartz equation
eGFR(ml/min/1.73m2)= length in cm x K
sr. creatinine(mg/dl)
K= 0.33 for premature infants
K= 0.45 for term infants to 1year
K= 0.55 for 1 year to 13 years
K= 0.70 in adolescent males ( females- 0.55)

44. Blood urea nitrogen
• Blood urea nitrogen is directly related to protein catabolism and inversely
related to glomerular filtration.
The reference interval is 8-20 mg/dl.
Plasma concentrations also tend to be slightly higher in males than females.
Measurement of plasma creatinine provides a more accurate assessment
than urea because there are many factors that affect urea level.
Non renal factors can affect the BUN level:
Mild dehydration
high protein diet
increased protein catabolism, muscle wasting as in starvation
GIT haemorrhage
Rhabdomyolysis

45. Clinical Significance
Condition associated with elevated levels of BUN are
referred to as azotemia.
Causes of BUN elevations:
Prerenal: renal hypoperfusion
Renal: acute tubular necrosis, glomerulonephritis
Postrenal: obstruction of urinary flow.

46. Uric acid
Renal handling of uric acid is complex and involves four
sequential steps:
Glomerular filtration of virtually all the uric acid in capillary
plasma entering the glomerulus.
Reabsorption of about 98 to 100% of filtered uric acid in PCT.
Subsequent secretion of uric acid into the lumen of the distal
portion of the proximal tubule.
Further reabsorption in the distal tubule.
Hyperuricemia is defined by serum or plasma uric acid
concentrations higher than 7.0 mg/dl (0.42mmol/L) in men or
greater than 6.0 mg/dl (0.36mmol/L) in women.

47. Plasma β2-microglobulin
It is present on the surface of most cells & in low concentrations in
the plasma.
It is completely filtered by the glomeruli and is reabsorbed and
catabolized by proximal tubular cells.
Being unaffected by diet or muscle mass, the plasma concentration
of β2-microglobulin is a good index of GFR in normal people.
It is increased in certain malignancies and inflammatory diseases.

48. Tubular function tests
Urine Concentration Test
The ability of the kidney to concentrate urine is a test of
tubular function.
That can be carried out readily with only minor inconvenience
to the patient.
This test requires a water deprivation for 12 hrs in healthy
individuals.
A specific gravity of > 1.02 or osmolarity >700 mOsm/kg
indicates normal concentrating power.
Specific gravity of 1.008 to 1.010 is isotonic with plasma and
indicates no work done by kidneys.
The test should not be performed on a dehydrated patient.

49. Vasopressin Test
More patient friendly than water deprivation test.
The subject has nothing to drink after 6 p.m. At 8 p.m five
units of vasopressin tannate is injected subcutaneously.
All urine samples are collected separately until 9 a.m the
next morning.
Satisfactory concentration is shown by at least one sample
having a specific gravity above 1.020, or an osmolality
above 600 mOsm/kg.
The urine/plasma osmolality ratio should reach 3 and
values less than 2 are abnormal.

50. Urine Dilution (Water Load) Test
After an overnight fast the subject empties his bladder
completely and is given 1000 ml of water to drink.
Urine specimens are collected for the next 4 hours& the patient
should completely empty his bladder on each occasion.
Normally the patient will excrete at least 700 ml of urine in the 4
hours, and at least one specimen will have a specific gravity less
than 1.004.
Kidneys which are severely damaged cannot excrete a urine of
lower specific gravity than 1.010 or a volume above 400 ml.
The test should not be done if there is oedema or renal failure;
water intoxication may result.

51. Biomarkers
• Biomarkers indicate renal injury before rise in serum
creatinine values.
• It would be helpful in patients at high risk of AKI.
 Role of biomarkers in AKI
• Differentiate from other types of kidney injury ( UTI,
glomerulonephritis, interstitial nephritis)
• Predict the outcome(need for RRT)
• Monitor response to intervention & treatment

52. AKI biomarkers

63. Preoperative assessment of the patient
with kidney disease

64. History
• Cause, nature and course of the disease process should be
ascertained
• Does this patient present with AKI, CKD or Acute on
chronic kidney failure?
• Cause of AKI should be sought:
- prolonged hypotension?
- sepsis/ rhabdomyolysis/nephrotoxic drugs
• What is the patient’s fluid balance over the preceding days?
• h/o Diabetes Mellitus and Hypertension?

65. In patients with known CKD, assess the stage of the disease.
If this is stage 5, does the patient receive RRT?
What modality of RRT?
When was RRT last provided, and when is the next due?
What is the patient’s ‘DRY WEIGHT’?
What is the urine output per day?
Clinical indications for urgent RRT
Acidosis
Electrolyte abnormalities
Intoxication
Oedema/fluid overload
Uremic consequenses

66. symptoms
• Infections- fever, chest symptoms, dysuria
• Obstruction- difficulties in voiding or incontinence
• Fluid overload- orthopnea, PND
• Palpitations
• Uremic and/or anaemic- lethargy, malaise, reduced
appetite

67. Clinical examination
• volume status- hypovolaemia/ fluid overload
• CVS- HR, BP, pericardial rub (uraemia) or abnormal
HS(gallop rhythm in heart failure)
• RS- Crepitations, tachypnoea
• Neurological- signs of uremia, peripheral neuropathy
• Hyperpigmentations & rashes- in CKD (vasculitis,
lupus)
• Assessment of potential sites for IV access

68. Investigations & Diagnostic Tools
• CBC – Anemia, leucocytosis, thrombocytopenia
• S. urea(15-45 mg/dl)
• S.Creatinine (0.6-1.3 mg/dl)
• Creatinine clearence (110-150 ml/min)
• Serum Electrolytes- Hyperkalemia
• Urinalysis
• CXR
• ECG & ECHO
• ABG- Metabolic acidosis, hypoxemia.

69. Pre Anaesthetic Optimisation
• Symptomatic and supportive treatment- hypotension,
hypovolemia, low cardiac output state- BP correction
• Treat underlying cause
• Correct fluids
• Electrolytes and acid-base derangements
• Dialysis

70. Monitoring
• All routine monitoring – ECG, NIBP, SpO₂, EtCO.
• Monitoring urinary output and intravascular volume
(desirable urinary output: 0.5 ml/kg/hr)
• Intra-arterial, central venous, pulmonary artery
monitoring are often indicated
• Intra-arterial blood pressure monitoring in poorly
controlled hypertensive patients

71. Pre-Medication
• Reduced doses of an opioid or BZD
• H2 blocker - Aspiration prophylaxis
• Metoclopramide -for accelerating gastric emptying,
prevent vomiting, ↓risk of aspiration
• Antihypertensive agents should be continued until the
time of surgery

72. Induction
Drugs Normal Dosages Altered Dosages
Thiopental 3-5 mg/kg 2-3 mg/kg
Propofol 1-2 mg/kg 1-2 mg/kg
Etomidate 0.2-0.4 mg/kg 0.2-0.4 mg/kg
Succinylcholine 1-2 mg/kg 0.5-1.5 mg/kg
Atracurium 0.6 mg/kg 0.6 mg/kg
Cisatracurium 0.15 mg/kg 0.15 mg/kg

73. Drugs Drugs safe Drugs safe in
limited or
reduced doses
Drugs
contraindicated
Premeditation Midazolam,
Temazepam
Diazepam
Induction Propofol, Etomidate thiopentone
Maintenance Desoflurane,
Isoflurane, Halothane
Sevoflurane Enflurane,
Methoxyflurane
Muscle Relaxants Sch, Atracurium,
Cisatracurim
Vecuronium,
Rocuronium
Pancuronium
Opioids Remifentanil, Fentanyl,
Alfentanil, Sufentanil
Morphine Pethidine
Local Anaesthetic Bupivacaine, Lidocaine
Analgesic Paracetamol opioids NSAIDS

74. Reversal
• Neuro-muscular blockade is reversed with Neostigmine or
pyridostgmine in combination with anticholenergic.
• Neostigmine and pyridostgmine has 50% & 70% renal elimination
respectively.
• Glycopyrolate has 80% renal excretion so should be used cautiously.
• Atropine undergoes 25% renal elimination and rest undergoes
hepatic metabolism to form metabolite noratropine which has renal
excretion.
• Extubation should be done after complete reversal of NM blockage.

75. Post Operative
• Monitoring of fluid overload or hypovolemia-titrate fluids
• Residual neuromuscular blockade
• Monitoring of urea and electrolytes
• ECG monitoring for detecting cardiac dysrhythmias
• Continue oxygen supplementation in post operative
period
• Analgesia
• Carefully titrated opioids, ↑CNS depression, respiratory
depression – naloxone.

76. REFERENCE
• Morgan & mikhail’s clinical anesthesiology 5th edition
• Stoelting’s pharmacology & physiology in anesthetic practice
• Miller’s anaesthesia 8th edition
• Clinical anesthesia, paul G.Barash, Bruce F.Cullen, Robert
K.Stoelting

78. Next seminar
Haemoglobinopathy and anaesthetic management
By Dr. Ankita Yashaswini(2nd yr PGT)