The kidneys are bean-shaped organs located in the retroperitoneal space that filter blood to produce urine. The functional unit of the kidney is the nephron, which contains a glomerulus for blood filtration and a tubule for reabsorption and secretion. Filtration occurs where glomerular capillaries are surrounded by Bowman's capsule in the renal corpuscle. Most reabsorption occurs in the proximal convoluted tubule under hormonal control. The loop of Henle and vasa recta create a medullary osmotic gradient for urine concentration. Urine is concentrated in the collecting duct by aquaporin water channels regulated by ADH.

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