RENAL PHYSIOLOGY BY DR.NANDHINI NACHIMUTHU DEPARTMENT OF ANAESTHESIOLOGY DR.RMLIMS

1. PRESENTOR: DR.NANDHINI NACHIMUTHU
DR.RMLIMS,LUCKNOW
DEPT.OF.ANAESTHESIOLOGY
RENAL
PHYSIOLOGY

2. ANATOMY
 Kidneys are a paired organs situated on the
posterior abdominal wall, one on each side
of the vertebral column, in the retroperitoneal
space.

3. LOCATION
 Extends from : T12 –L3 vertebra
 Size : 11 cm long, 6 cm broad, 3 cm thick
 Weight : 150g in males
130g in females
 Colour : Reddish –brown
 Shape : Bean-shaped

4. ANTERIOR RELATIONS

5. POSTERIOR RELATIONS

6. BLOOD SUPPLY

7.  NERVE SUPPLY :
• Renal plexus (Coeliac plexus )
• Sympathetic fibres-T10 – L1 (Vasomotor)
 LYMPHATIC DRAINAGE :
• Para-aortic nodes

8. THE NEPHRON
• Functional unit of kidney- Nephron
Glomerulus
Bowman’s capsule
Proximal convoluted tubule
The loop of Henle
Distal convoluted tubule
The collecting tubule
Juxtaglomerular apparatus

10. • Nephrons- 2 types :
 Cortical nephrons
(closer to the surface-Cortex)
 Juxtamedullary nephrons
(have tubules that descend into medulla)

11. THE GLOMERULUS
 Tufts of capillaries
surrounded by Bowman’s
capsule
• Parietal layer
• Bowman’s space
• Visceral layer
 Glomerular capillaries
are unique(interposed
b/w 2 sets of arterioles)

12. RENAL CORPUSCLE

13. • GLOMERULAR FILTRATION BARRIER:
Filtration slits:
• Endothelial cells:
70-100 nm
• Epithelial cells :
25-40 nm

14. GLOMERULAR CAPILLARY PRESSURE:
 Function of vascular activity of both arterioles
 Favors glomerular filtration
 Causes water & LMW-substances to be filtered into
Bowman’s capsule & tubule system.
GLOMERULAR FILTRATE
 Composition-similar to plasma but without plasma
proteins & cellular elements

16. PROXIMAL CONVOLUTED TUBULE
 65-75% of ultrafiltrate –Reabsorbed
 Major function : Sodium reabsorption
• Actively transported out of PCT at their capillary
side by membrane-bound Na+-K+-ATPase
• Low intracellular concentration of Na+
• Passive movement of Na+ down its gradient
from tubular fluid into epithelial cells.

17.  Na+ reabsorption:
- Angiotensin II & Norepinephrine
- Dopamine & Fenoldopam
 Coupled with reabsorption of other solutes &
secretion of H+ responsible for
reabsorption of 90% of filtered bicarbonate ions
 Chloride reabsorption:
• Active K+-Cl- cotransporter
• Passive Traverse tight junctions

19.  Water moves passively out along osmotic
gradient
 Apical membranes of epithelial cells contain
specialized water channels : Aquaporin-1
(facilitate water movement)
 Secretes organic cations & anions.
 LMW proteins,which are filtered by glomeruli,
are normally reabsorbed by proximal tubular
cells to be metabolized intracellularly.

20. OVERALL FUNCTION OF PCT
 Reabsorption of:
• All filtered glucose, amino acids, vitamins,
protein & Kreb’s cycle intermediates.
• 2/3rd of filtered load of Na+ & water.
• 90% of the filtered load of HCO3
- .
• 80% of the filtered inorganic phosphate.
• Variable amount of K+, Ca2+, Mg2+ & urea.
 Secretion of :
• Organic solutes as PAH, drugs, various amines
and ammonia.

21. LOOP OF HENLE
 Consists of descending &
ascending portions
Maintain hypertonic
medullary interstitium
 Countercurrent mechanism

22. COUNTERCURRENT MECHANISM
 The ability of kidneys to produce either
dilute or concentrated urine depends on the
gradient in osmolarity b/w renal cortex &
medulla that is created by Loop of Henle
 Countercurrent Multiplier : LOH
 Countercurrent Exchanger : Vasa Recta

23.  THIN DESCENDING LIMB:
-Permeable to water
-Impermeable to ions & urea
 THIN ASCENDING LIMB :
-Permeable to ions & urea
-Impermeable to water
 THICK ASCENDING LIMB :
-Impermeable to water
-Moves ions via secondary active transport
involving luminal Na+-K+-2Cl- cotransporters

24.  OSMOLARITY of filtrate entering:
• Descending limb of LOH: Iso-osmolar
• Distal convoluted tubule: Hypo-osmolar
• Renal medullary intersitium: Hyper-osmolar
 LOH-Highly metabolically active
(requires good blood supply)
Osmolarity in renal medulla :

25. VASA RECTA
 Specialised blood supply of LOH
 Arteriolar branches of efferent arterioles
Follow the LOH deep into medulla
Descends with ascending LOH
Turns a hairpin bend
Ascends with descending LOH
Forming countercurrent flow of blood

28. ROLE OF UREA
 Urea –freely filtered at glomerulus & then reabsorbed
along the tubule
 40% of filtered urea-cleared into urine
 Remaining-contributes to high osmolarity of
medullary interstitium
 UREA TRANSPORTERS :
• UT-A1,UT-A3 : Inner medullary collecting duct
• UT-A2 : Thin descending LOH
• UT-B : Descending Vasa Recta

29.  In PCT : 50% of filtered urea – Reabsorbed
 In LOH :
• Concentration of urea : Higher
(Renal medullary interstitium > Tubule)
• Urea diffues into tubular fluid : Facilitated
diffusion
• 50% of filtered urea – secreted by thin & thick
ascending limb of LOH
 In IMCD :Urea is reabsorbed by facilitated
diffusion from collecting duct into interstitium

31. DISTAL CONVOLUTED TUBULE
 Receives hypotonic fluid from the LOH
 Responsible for only minor modifications of tubular
fluid
 In contrast to more proximal portions,
distal nephron has numerous tight junctions b/w
tubular cells relatively impermeable to water & sodium.
 Maintain the gradients generated by the LOH

32. OVERALL FUNCTION OF DCT
Reabsorption :
• 7-10% of filtered load of Na+
• 10-15% of filtered lead of H2O
Secretion : variable amount of H+ & K+
Major control site for Na+, K+, Ca2+ & acid-
base balance of body.
- Controlled by hormones
• Na reabsorption - Aldosterone
• H2O reabsorption - ADH
• Calcium reabsorption - PTH & vitamin-D

33. COLLECTING TUBULE
 Divided into :
Cortical & Medullary portions
 CORTICAL COLLECTING TUBULE :
2 cell types :
• Principal (P) cells- secrete K+ & aldosterone-
stimulated Na+ reabsorption
• Intercalated (I)cells-Acid-base regulation

34. MEDULLARY COLLECTING TUBULE:
 The high osmolarity in medulla allows for quick
reabsorption of water by osmosis mediated by
AQUAPORINS:
• Tetramer protein Channels that facilitate rapid
passage of water across lipid cell membranes
• Found in : kidneys, brain, salivary & lacrimal
glands & respiratory tract.
• Aquaporin-1- proximal renal tubules
• Aquaporin-2- renal collecting ducts.

35.  Principal site of action :
Antidiuretic hormone (ADH/AVP)
Activates adenylate cyclase
Genarates cAMP
Increases permeability of cell membranes to water
epithelial cells lining CD
ADH INCREASED DECREASED
WATER
REABSORPTION
URINE CONCENTRATED DILUTED

36. JUXTA-GLOMERULAR APPARATUS
 Situated where distal
renal tubule passes b/w
afferent & efferent
arterioles.
 Epithelial cells of the
distal renal tubules that
contact these arterioles
Macula Densa
 Corresponding cells in
the arterioles:
Juxtaglomerular cells

37.  Release of renin depends on :
• β1 stimulation
• Changes in afferent
arteriolar wall pressure
• Changes in chloride flow past
the macula densa
 FUNCTION :
• Synthesis, store and release of Renin
• Acts as Baroreceptors
(detect tension in afferent arteriolar wall)

39. TUBULAR TRANSPORT MAXIMUM
 Maximum amount of a substance that can
be actively reabsorbed from the lumens of
renal tubules each minute.
 Depends on :
• Amounts of carrier substance
• Enzyme available to the specific active
transport system in lining epithelial cells of
renal tubules.

40. For glucose:
220-375 mg/min
Loss of glucose in urine
occurs at
concentrations above
Tm for glucose.
(+) of large amounts of
unreabsorbed solutes
in urine
Osmotic diuresis
TMAX

41. RENAL BLOOD FLOW
 0.5% Total body weight
 20–25% Total cardiac output.
 400 mL/100 g/minute (or) 1-1.25 L/min
NEPHRON
S
CORTICAL JUXTAMEDULLARY
RBF 90% 10%
(vulnerable to ischemia)
FUNCTION  Flow-dependent
functions
 Filtration &
tub.reabsorption
 High interstitial fluid
osmolarity
 Concentration of urine

42. INTRAVASCULAR PRESSURES

43. RENAL CORTEX –Blood flow
 Renal artery
 Afferent arterioles
 Glomerular capillaries
 Efferent arterioles
 Peritubular capillaries
HIGH PERSSURE
SYSTEM
LOW PRESSURE
SYSTEM

44. RENAL MEDULLA-Blood flow
 Capillaries that descend with the loops of Henle
– Vasa Recta
 Descend into medulla
Return to cortex
Empty into veins.
 Help in : Formation of concentrated urine
(countercurrent mechanism)
Receive 1-
2% of RBF

45. AUTOREGULATION OF RBF
 Occurs at: MAP 60-
160 mm Hg
 RBF & GFR are kept
relatively constant by
afferent arteriolar
vasoconstriction or
vasodilation
 Ceases: MAP
< 40-50 mm Hg

46. MYOGENIC THEORY TUBULOGLOMERULAR
FEEDBACK
Perfusion pressure
Wall tension in afferent
arterioles
Contraction of smooth
muscle in vessel wall
Resistance of vessels
RBF & GFR-Constant
Perfusion pressure
Filtration
NaCl delivery to
macula densa
Releases factors
Resistance of vessels
RBF

47.  If decreased effective circulating volume,
RBF may be decreased despite adequate
perfusion pressure
 Activation of the sympathetic system shunts
cardiac output away from kidneys.
 Hence, adequate BP does not necessarily
indicate adequate renal perfusion
(in presence of hypovolemia)

48. Measurement of RBF
 Renal plasma flow (RPF) : most commonly
measured by p-aminohippurate clearance
 PAH : Completely cleared from plasma
 RPF =Clearance of PAH= * Urine flow
RBF=
[PAH]U
[PAH]P
RPF
1-Hematocrit
 Normally, RPF 660 ml/min
RBF 1200 ml/min

49. GLOMERULAR FILTRATION RATE
 The volume of fluid filtered from the glomerular
capillaries into Bowman’s capsule per unit time
 Normally, GFR : ~125 ml/min (or) 180 L/D
 99% of glomerular filtrate : Reabsorbed
(So, daily urine output is 1 to 2 L)

50. NET FILTRATION PRESSURE

51. FACTORS AFFECTING GFR
 Renal blood flow
 Glomerular capillary hydrostatic pressure
 Hydrostatic pressure in Bowman’s capsule
 Glomerular capillary permeability
 Effective filtration surface area
 Afferent or efferent arteriolar constriction
 Systemic blood pressure
 Ureteral obstruction
 Edema of kidney inside tight renal capsule
 Concentration of plasma proteins

53. MEASUREMENT OF GFR
 Inulin clearance-most accurate
 Creatinine clearance-most commonly used
 COCKCROFT-GAULT FORMULA:

54.  Creatinine clearance =
[Urine]Cr * Volume
[Plasma]Cr
 Filtration fraction =
GFR
RPF
• Normally, FF = 20%
• Fraction of plasma that is
filtered by glomerulus

55. REGULATION OF RBF & GFR
 Intrinsic autoregulation
 Tubuloglomerular balance & feedback
 Hormonal regulation
 Neurocrine & Paracrine regulation

56. HORMONAL REGULATION :
 Angiotensin II
 Epinephrine & Norepinephrine
 Prostaglandins
 Atrial natriuretic peptide (ANP)

57. NEURONAL REGULATION :
 Sym.outflow (T4–L1) –celiac & renal plexus.
 Innervation:
β1-JG apparatus
α1-Renal vasculature
 α1 Na+ reabsorption in PCT
 α2 Na+ reabsorption & promote water
excretion.
 Dopamine & fenoldopam dilate afferent &
efferent arterioles (D1)

58. SODIUM HANDLING
 CHANGES IN GFR :
• Plasma volume - GFR - Na+ filtered
& excreted in urine
• Plasma volume - Na+ is conserved through
reduced GFR
 CHANGES IN Na+ REABSORPTION :
1)Bulk reabsorption in PCT & LOH
2) Reabsorption in DCT & Collecting duct
(Controlled by Aldosterone)

59. Bulk reabsorption in PCT & LOH :
 60% of filtered Na+ - Reabsorbed in PCT
-Driven by : Basolateral Na+-K+-ATPase pump
-Reabsorbed from tubular lumen by:
Passive diffusion, Co-transport with
glucose,Counter-transport with H+
 30% of filtered Na+- Reabsorbed in LOH
- Through Na+-K+-2Cl- co-transporter

60. Reabsorption in early DCT:
 90% of filtered Na+ - already reabsorbed before
filtrate reaches DCT
 Intracellular [Na+] –kept low as a result of
basolateral Na+-K+-ATPase
• Na+ transfer across tubular cell luminal
membrane-controlled by ALDOSTERONE
1) In DCT :
5% of filtered Na+ -Reabsorbed through Na+-Cl-
co-transporter in luminal membrane

61. 2) In late DCT & Collecting duct :
• Aldosterone acts on 2 different cell types:-
PRINCIPAL CELLS INTERCALATED CELLS
 Reabsorb Na+
 Secrete K+
 Reabsorb Na+
 Secrete H+
 Acts on Na+-K+
countertransporter
 Acts on Na+-H+
countertransporter
• Combined effect of Aldosterone on these cells:
Reabsorption of Na+ & H2O & Secretion of K+ & H+

63. POTASSIUM HANDLING
 K+ - Freely filtered at glomerulus
 All of filtered K+ -Reabsorbed in:
• PCT - Diffusion
• LOH - Na+-K+-2Cl- co-transporter
Irrespective of whether body K+ -High/Low
Plasma K+ - Regulated by its
secretion in DCT & CD

64. • When plasma K+ concentration,
LOW HIGH
Additional K+-
Reabsorbed in
DCT through
H+-K+-ATPase
In total,
upto 99% of K+ -
Reabsorbed
 Adrenal cortex-directly
stimulated to secrete
Aldosterone
 Reabsorbs Na+ & H2O
 Secretes H+ & K+
DCT CD