Renal anatomy and physiology seminar and chronic and acute kidney failure

1. RENAL PHYSIOLOGY
BY
DR. PRATEEK GUPTA
PG (ANESTHESIA) 1st YEAR

3. A WET BED
• A – maintaining ACID-BASE balance
• W – maintain WATER balance
• E – ELECTROLYTE balance
• T – TOXIN removal
• B – BLOOD PRESSURE control
• E – making ERYTHROPOETIN
• D – vitamin D metabolism

4. ANATOMY
• BEAN SHAPED
• REDDISH BROWN ORGAN
• WEIGHT – 135g (females)
150g (males)
• LENGTH - 10-15cm, WIDTH – 5-7.5cm
• RETROPERITONEAL ORGAN
• T11-L3
• RIGHT KIDNEY USUALLY SHORTER THAN LEFT (max
1.5cm)

5. • The left kidney lies slightly above the right
kidney.
• RIGHT KIDNEY USUALLY SHORTER THAN LEFT
(max 1.5cm)

7. Click to add title
• RENAL CAPSULE Coverering of a tough capsule
of fibrous connective tissue-
• Adhering to the surface of each kidney-two
layers of FAT to help cushion them.
• LAYERS - outer cortex and inner medulla

8. RENAL CORTEX
• Outer granular layer of
the kidney that
contains most of the
nephrons
• Red in color
• Highly vascular
• Contains bowmans
capsule and convolated
tubules

9. RENAL MEDULLA
• Pink in colour
• Less vascular
• Radially Striated appearance
• Contains largely the straight running portions
of the nephrons
• contains renal pyramids, renal papillae, renal
columns, renal calyces (minor/major),renal
pelvis and part of nephron, not located in the
cortex
• Site for salt, water and urea absorption

10. • RENAL PYRAMID-
Triangular shaped unit in
the medulla
• houses the loop of Henle
and collecting duct of the
nephron
• RENAL COLUMN
– Area between the
pyramids, located in the
medulla
– Used as a space for blood
vessels

11. • RENAL PAPPILAE
• The tips of the renal pyramids
release urine into the calyces
• RENAL CALYCES
• Collecting sacs that surround
the renal papillae
• Transport urine from renal
papillae to renal pelvis

12. • RENAL PELVIS
• Cavity which lies in the centre of the kidney
and which extends into the ureter
• Collects urine from all of the calyces in the
kidney
• HILUS – renal artery and renal nerve enter
through this and renal vein exit from here,
lymphatic and ureter leaves through this region

13. NERVE SUPPLY
• Renal plexus from coeliac plexus
• Sympathetics from T10-L1
• Afferents from T10-T12

15. NEPHRON
• Structural and functional unit of the kidneys
• Inside each kidney, there are about 1 million
nephrons
• Never divide
• 5 cm long
• Total lengths- 100 kms

16. TYPES OF NEPHRON
• CORTICAL
-The loop of Henle does not extend past the
cortex of the kidney.
• JUXTA MEDULLARY
- Loop of Henle extends past the cortex and
into the medulla of the kidney

18. PARTS OF NEPHRON
• GLOMERULUS- consists of tuft of capillaries
surrounded by bowman’s capsule
• The site for blood filtration
• operates as a nonspecific filter - removes both useful
and non-useful material
• the product of the glomerulus – ULTRAFILTRATE
• BOWMAN’S CAPSULE
– A sac that encloses
– glomerulus
– transfers filtrate from the glomerulus to the Proximal
Convoluted Tubule (PCT)

19. • Afferent Arteriole
• Transport arterial blood to glomerulus for
filtration
• Efferent Arteriole
• Transports filtered blood from glomerulus
through the peritubular capillaries and the
vasa recta, and to the kidney venous system

20. • PERITUBULAR ARTERIES
• transport reabsorbed materials from the PCT and
DCT into kidney veins and eventually back into the
general circulation
• help complete the conservation process
(reabsorption) that takes place in the kidney

21. RBF
• 25% of total CO
• 400ml/gm/min
• 90% to cortex
• is directly proportional to the pressure
difference between the renal artery and the
renal vein, and is inversely proportional to the
resistance of the renal vasculature.

22. • Vasoconstriction of renal arterioles, which
leads to a decrease in RBF, is produced by acti-
vation of the sympathetic nervous system and
angiotensin II.
• At low concentrations, angiotensin II
preferentially constricts efferent arterioles,
thereby “protecting” (increasing) the GFR.
• RBF= RPF/(1- Hematocrit)

23. GFR
• Volume of collective infiltrate formed over time
• 125 ml/min or 180 l/day
• 99% of It is reabsorbed
• INULIN
GFR= UV/P

24. STARLING FORCES
• The driving force for glomerular filtration is the
net ultrafiltration pressure across the
glomerular capillaries.
• GFR can be expressed by the Starling equation:
• GFR=Kf [(PGC −PBS )−(πGC −πBS )]
• Kf is the filtration coefficient

25. • PGC which is constant along the length of the capillary.
-increased by dilation of the afferent arteriole or
constriction of the efferent arteriole.
Increases in PGC cause increases in net ultrafiltration
pressure and GFR.
- 60 mm of Hg
• PBS is increased by constriction of the ureters.
Increases in PBS cause decreases in net
ultrafiltration pressure and GFR.
- 18 mm of hg

26. • πGC
- increases along the length of the glomerular
capillary because filtration of water increases the
protein concentration of glomerular capillary blood.
It is increased by increases in protein
concentration.
32 mm of Hg
• πBS
• It is usually zero, and therefore ignored, because
only a small amount of protein is normally filtered.

27. AUTOREGULATION
• Feedback mechanish intrinsic to kidney
• Keeps RBF and GFR relatively constant despite
changes in arterial pressure
• Range 70-160 mm of Hg
• accomplished by changing renal vascular
resistance
• Two mechanisms
- MYOGENIC
- TUBULO-GLOERMULAR

28. MYOGENIC
• Renal afferent arterioles contract in response to
stretch. Thus, increased renal arterial pressure
stretches the arterioles, which contract and
increase resistance to maintain constant blood
flow.
• Rapid, 3-10 seconds
• Absent in efferent arterioles (absence of voltage
gated ca+ channels ??)

30. TUBULOGLOMERULAR
• increased renal arterial pressure leads to
increased delivery of fluid to the macula
densa. The macula densa senses the increased
load and causes constriction of the nearby
afferent arteriole, increasing resistance to
maintain constant blood flow.
• links sodium and chloride concentration at the
macula densa with control of renal arteriolar
resistance.

33. ATRIAL NATRIURETERIC PEPTIDE
• Secreted by heart muscle cells
• Released by atrial myocytes in response to high
increased pressure and volume
• Powerful vasodilator
• Binds to receptors in renal collecting ducts
inhibiting sodium reabsorption and hence
decrease in circulating volume
• Neutral endopeptidase (NEP) and omapatrilat

34. Effects of ANP on renal
• Dilates afferent arteriole
• Constricts efferent arteriole ( hence increasing
GFR and more excretion of sodium and
potassium)
• Increases blood flow through vasa recta, hence
washes out solutes
• Decreases Na reabsorption in DCT and CCD via
cGMP dependent phosphorylation of EnaC
• Inhibits renin and aldosterone secretion

35. • Arterial Pressure
• Glomerular Filtration Pressure GFR
Na and water retention by PCT
• Na delivery at Macula Densa
• Signal to Afferent arteriole
• Adenosine/ATP
Aff A Resistance Vasodilation of AA
• Renin Angiotensin II
• Eff A Resistance Vasoconstriction of EA

36. JUXTAGLOMERULAR APPARATUS
• specialized region of a nephron where the
afferent arteriole and Distal Convoluted
Tubule (DCT) come in direct contact with each
other.
- Juxtaglomerular cells
- Macula densa cells
- Extraglomerular mesangial cells (Lacis
cells)

39. JG CELLS
• modified smooth muscle cells) of afferent
arteriole including renin containing (synthesizes
and stores renin) and sympathetically innervated
granulated cells which function
as mechanoreceptors to sense blood pressure.

40. Macula densa cells
• (Na+ sensors) of Distal Convoluted Tubule
(DCT) which function as chemoreceptors to
sense changes in the solute concentration and
flow rate of filtrate.

41. Extraglomerular mesangial cells (Lacis
cells)
• forming connections via actin and
microtubules which allow for selective
vasoconstriction/vasodilation of the renal
afferent and efferent arterioles with mesangial
cell contraction.

42. Uses
• Local transmission of Tubuloglomerular
Feedback (TGF) at its own nephron via
angiotensin II (AT II)
• Systemic production of Angiotensin II (AT II) as
part of Renin-Angiotensin-Aldosterone System
(RAAS)
•

43. URINE FORMATION
• Flitered load
• Excreted load
• Tubular transport maximum

44. TUBULAR TRANSPORT MAXIMUM
• Maximum amount of substance that can be
actively reabsorbed from renal tubules in a
minute
• Depends on
-carrier substance
-enzyme available

45. GLUCOSE
• Reabsorption
• Na+–glucose cotransport in the proximal tubule
reabsorbs glucose from tubular fluid into the
blood
• At plasma glucose concentrations less than 250
mg/dL, all of the filtered glucose can be
reabsorbed because plenty of carriers are
available; in this range, the line for reabsorption
is the same as that for filtration.
•
•

46. • At plasma glucose concentrations greater than 350
mg/dL, the carriers are saturated.
• Therefore, increases in plasma concentration above
350 mg/dL do not result in increased rates of
reabsorption.
• The reabsorptive rate at which the carriers are
saturated is the Tm.

47. • At plasma concentrations less than 250mg/dL, all
of the filtered glucose is reabsorbed and
excretion is zero. Threshold (defined as the
plasma concentration at which glucose first
appears in the urine) is approximately 250
mg/dL.
• At plasma concentrations greater than 350
mg/dL, reabsorption is saturated (Tm).
• Therefore, as the plasma concentration
increases, the additional filtered glucose can- not
be reabsorbed and is excreted in the urine.

48. SODIUM
• Na+ is freely filtered across the glomerular
capillaries; therefore, the [Na+] in the tubular fluid
of Bowman’s space equals that in plasma (i.e.,
TF/PNa+ = 1.0).
• Na+ is reabsorbed along the entire nephron, and
very little is excreted in urine (<1% of the filtered
load).

50. EARLY PCT
• 67%
• Permeable to water

51. Thick ascending loop of henle
• 25%
• Impermeable to water
• Diluting segment
• Na-k-cl channel

53. DCT AND CD
• together reabsorb 8% of the filtered Na+.
• a. Earlydistaltubule—special features
• reabsorbs NaCl by a Na+-Cl- cotransporter.
• is impermeable to water
• Late distal tubule and collecting duct
• (1) Principal cells
– reabsorb Na+ and H2O.
– Secrete K+.
•

55. • Aldosterone increases Na+ reabsorption and
increases K+ secretion.
• the action of takes several hours to develop
because new protein synthesis of Na+
channels (ENaC) is required.
• About 2% of overall Na+ reabsorption is
affected by aldosterone.
• .

56. • (2) α-Intercalated cells
– Secrete H+by an H+-adenosine
triphosphatase(ATPase),which is stimulated by
aldosterone.
– Reabsorb K+ by an H+,K+-ATPase.

57. • Anti diuretic hormone (ADH) increases H2O
permeability by directing the insertion of H2O
channels in the luminal membrane.
• In the absence of ADH, the principal cells are
virtually impermeable to water

58. POTASSIUM
• K+ is filtered, reabsorbed, and secreted by the
nephron.
• K+ excretion can vary widely depending on
dietary K+ intake, aldosterone levels, and
acid–base status.

60. PCT
• Reabsorbs 67% of the filtered K+ alongwith
Na+ and H2O.
• THICK ASCENDING LOOP OF HENLE
• Reabsorbs 20% of the filtered K+.
Reabsorption involves the Na+–K+–2Cl–
cotransporter in the thick ascending limb

61. DCT AND CD
• either reabsorb or secrete K+, depending on
dietary K+ intake.
• Reabsorption of K+
• involves an H+,K+-ATPase in the luminal membrane
of the α-intercalated cells.
• occurs only on a low-K+ diet (K+ depletion). Under
these conditions, K+ excretion can be as low as 1%
of the filtered load because the kidney conserves
as much K+ as possible.

62. • SECRETION
• occurs in the principal cells.
• Aldosterone
– Increases K+ secretion.
– The mechanism involves increased Na+ entry into the
cells across the luminal membrane and increased
pumping of Naout of the cells by the Na+−K+ pump.
– Stimulation of the Na+–K+ pump simultaneously increases
K+ uptake into the principal cells, increasing the
intracellular K+ concentration and the driving force for K+
secretion. Aldosterone also increases the number of
luminal membrane K+ channels.

63. Acid–base
– Effectively, H+ and K+ exchange for each other across the
basolateral cell membrane.
– Acidosis decreases K+secretion.The blood contains excess
H+;therefore,H+ enters the cell across the basolateral
membrane and K+ leaves the cell. As a result, the intracellular
K+ concentration and the driving force for K+ secretion
decrease.
– Alkalosis increases K+ secretion. The blood contains too little
H+; therefore, H+ leaves the cell across the basolateral
membrane and K+ enters the cell. As a result, the intracellular
K+ concentration and the driving force for K+ secretion increase.

64. Luminal anions
• Excess anions (e.g., HCO3–) in the lumen
cause an increase in K+ secretion by increasing
the negativity of the lumen, which favors K+
secretion.

66. UREA
• Fifty percent of the filtered urea is reabsorbed
passively in the proximal tubule
• The distal tubule, cortical collecting ducts, and outer
medullary collecting ducts are impermeable to urea;
thus, no urea is reabsorbed by these segments.
• ADH increases the urea permeability of the inner
medullary collecting ducts.Urea reabsorption from
inner medullary collecting ducts contributes to urea
recycling in the inner medulla and to the development
of the corticopapillary osmotic gradient.
• Urea excretion varies with urine flow rate .

67. • Glomerular filtration
• Tubular reabsorption
• Tubular secretion

68. COUNTER CURRENT
• process of using energy to generate an osmotic
gradient that enables you to produce
concentrate urine
• The vasa recta capillaries are long, hairpin-
shaped blood vessels that run parallel to the
loops of Henle.
• The hairpin turns slow the rate of blood flow,
which helps maintain the osmotic gradient
required for water reabsorption along with loop
of henle

71. • The three segments of the loops of Henle have
different characteristics that enable countercurrent
multiplication.
• The thin descending limb is passively permeable to
both water and small solutes such as sodium chloride
and urea.
• As active reabsorption of solutes from the ascending
limb of the loop of Henle increases the concentration
of solutes within the interstitial space (space between
cells), water and solutes move down their
concentration gradients until their concentrations
within the descending tubule and the interstitial space
have equilibrated. As such, water moves out of the
tubular fluid and solutes to move in. This means, the
tubular fluid becomes steadily more concentrated or
hyperosmotic (compared to blood) as it travels down
the thin descending limb of the tubule.

72. • The thin ascending limb is passively permeable to
small solutes, but impermeable to water, which
means water cannot escape from this part of the
loop. As a result, solutes move out of the tubular
fluid, but water is retained and the tubular fluid
becomes steadily more dilute or hyposmotic as it
moves up the ascending limb of the tubule.
•

73. • The thick ascending limb actively reabsorbs sodium,
potassium and chloride. this segment is also
impermeable to water, which again means that water
cannot escape from this part of the loop. This segment
is sometimes called the “diluting segment”.
• The length of the loop of Henle determines the size of
the gradient - the longer the loop, the greater the
osmotic gradient.
•

74. • Absorbed water is returned to the circulatory
system via the vasa recta, which surrounds the
tips of the loops of Henle. Because the blood flow
through these capillaries is very slow, any solutes
that are reabsorbed into the bloodstream have
time to diffuse back into the interstitial fluid,
which maintains the solute concentration
gradient in the medulla. This passive process is
known as countercurrent exchange.
•

75. UREA RECYCLING
• Urea recycling in the inner medulla also contributes to
the osmotic gradient generated by the loops of Henle.
• Antidiuretic hormone increases water permeability, but
not urea permeability in the cortical and outer
medullary collecting ducts, causing urea to concentrate
in the tubular fluid in this segment.
• In the inner medullary collecting ducts it increases both
water and urea permeability, which allows urea to flow
passively down its concentration gradient into the
interstitial fluid. This adds to the osmotic gradient and
helps drive water reabsorption.
•

76. ADH
• stimulates NaCl reabsorption in the thick ascending
limb. Therefore, increases corticopapillary osmotic
gradient.
• Urea recycling ADH increases the H2O permeability
of the principal cells of the late distal tubule.
• H2O is reabsorbed from the tubule until the
osmolarity of distal tubular fluid equals that of the
surrounding interstitial fluid in the renal cortex (300
mOsm/L).
• ADH increases the H2O permeability of the principal
cells of the collecting ducts.

78. Measurement of kidney function
• Cockcroft-gault formula
• GFRmen = [(140-age) x weight]/(sr. cr x 72)
• GFRwomen=[(140-age) x weight x 0.85]/(sr.crx72

79. ACUTE KIDNEY INJURY
• Abrupt reduction in kidney’s ability to eliminate
nitrogenous waste products and mainatain
electrolyte and fluid homeostasis
• Pathophysiologically can be classified as
• PRERENAL
• INTRINSIC
• POST RENAL

80. PRERENAL• decrease in renal function due to hypoperfusion
despite intact glomeruli and tubules
• CAUSES
• Severe blood loss
• low blood pressure related to major cardiac or
abdominal surgery, severe infection (sepsis), or injury.
• Severe dehydration caused by excessive fluid loss.
• Severe burns.
• Medications (NSAIDS and calcineurin#)

81. INTRINSIC
• Direct damage to kidney
• Most common ACUTE TUBULAR NECROSIS (ATN)
• Other causes acute glomerulonephritis and acute
interstitial nephritis
• ATN can be ischemic or due to toxic agents
• ATN secondary to renal medullary ischemia is the
most common peri-operative cause of AKI
- adequate urine output can be falsely assuring
- there Na-K ATPase failure leading to inability
to concentrate urine

82. POST RENAL
• Aka obstructive nephropathy
• Causes
- renal stones
- prostatic hypertrophy
- mechanical obstruction

83. RIFLE
• R – Risk of renal dysfunction
• I – Injury to the kidneys
• F – Failure of kidney function
• L – loss of kindey function, needing renal
replacement therapy for more than 4 weeks
• E – End stage kidney disease, needing
hemodialysis for more than 3 months

85. NGAL
• Can be measure either in blood or urine soon
after injury
• cut off value 150ng/ml
• Can used for prediction of both presence and
severity of AKI in cardiac surgery
• Predict delayed graft rejection after kidney
transplant

86. • Cystatin c
• IL-8
• KIM-1 (kidney injury molecule)

87. • Anesthetic drugs have significant
hemodynamic effect either by reducing SVR,
depressing myocardiac function or decreasing
effective preload
• Highly sensitive to sympathetic stimulation
(pain, surgical or catecholamines)
- leads to increases renal vasculature
resistance, hence shunting of blood
- constriction of afferent arteriole leading to
decreased GFR to the point that urine drops to
zero

88. • Painful stimuli can lead to release of AVP
• AVP and aldosterone tend to restore normal
circulation volume by retaining Na and water.
• Autoregulation of RBF may be effected in case of
sustained changes MAP (>10 minutes)
•

89. PERIOP ASSESMENT
• AGE >56 YEARS
• MALE
• ACUTE CHF
• ASCITES
• DIABETES
• HTN
• SURGICAL RISKS (INTRAPERITONEAL AND
EMERGENT OPERATIONS)

90. • CARDIO-PULMONARY BYPASS
Due to alteration
- RBF
- Inflammatory response
- Microemboli
- direct toxicity
Clamping of aorta in is a/w atheromatous emboli
to kidney
Valve surgery > CABG

91. MANAGEMENT• Minimize exposure to nephrotoxic drugs
• Maintain RBF
- correct intravascular volume depletion
- maintain systemic arterial pressure
• optimize CHF and maintain adequate CO peri-
operatively
• In lap surgery use minimum possible abdominal
suffation pressure
• Adequate analgesia (minimize sympathetic stimulation)
• Lose dose dopamine doesn’t prevent or AKI or improve
mortality
Fenoldopam?