Renal physiology-1

1. Dr. Osama El-Shahat
Consultant Nephrologist
Head of Nephrology Department
New Mansoura General Hospital (international)
ISN Educational Ambassador

2. BASIC AGAIN AND AGAIN

3. Lecture Outline
 Introduction
 Functions of the kidney
 Renal circulation & renal blood flow
 Physiological anatomy of the kidney
 Nephron & its types

4.  A retroperitoneal organ
 T11-L3
 Normal size: 11-15cm in adults.
 located in the upper region of the
abdominal cavity just above the
waistline.
 protected by the ribcage.
 Right kidney usually shorter than
the left (upper limit of variation in
length between right & left 1.5
cm)

5.  1- Execratory function:
a. Metabolites
b. drugs
c. toxins
 2- Homeostatic function:
a.Maintenance of water balance.
b.Maintenance of electrolyte balance.
c.Maintenance of acid-base balance.

6.  3- Endocrine (hormonal) secretory function:
a)Renin by the juxtaglomerular cells (JG)
b)Erythropoietin hormone by endothelial
cells of peritubular capillaries of renal
cortex
c)Prostaglandins.
 4- Endocrine (hormonal) metabolic function:
The kidney converts vitamin D3 → active
1,25dihydroxycholecalciferol by alpha one
hydroxylase enzyme in cells of PCT under
effect of PTH.

7. Kidneys
Ureters
Urinary Bladder
Urethra
– The functional unit of the system
Conducting & Storage
components

10. Kidneys and their structures
The Renal Arteries
 transport oxygenated
blood from the heart and
aorta to kidneys for
filtration
The Renal Veins
 Transport the filtered,
deoxygenated blood
from kidneys to the
posterior vena cava and
finally the heart

11. Kidneys and their structures
Renal Capsule
(inferior/superior)
 Outer membrane which
encloses and protects kidneys
against infections and trauma.
The Renal Cortex
 Outer layer (granulated) of the
kidney that contains most of
the nephrons.

12. Kidneys and their structures
The Renal Medulla
 Inner layer (radially striated) of the kidney
 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

13. Kidneys and their structures
The Renal Pyramid
 Triangular shaped unit in the
medulla
 houses the loop of Henle and
collecting duct of the nephron
The Renal Column
 Area between the pyramids,
located in the medulla
 Used as a space for blood vessels

14. Kidneys and their structures
The Renal Papillae
 The tips of the renal
pyramids
 release urine into the
calyces
The Renal Calyces
 Collecting sacs that
surround the renal papillae
 Transport urine from renal
papillae to renal pelvis

15. Kidneys and their structure
The 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

16. Kidneys and their structures
 The Ureters (right/left)
 Tubes that transports urine
from the renal pelvis to the
bladder
 The Urinary Bladder
 Hollow, expandable, muscular
organ located in the pelvic
girdle
 Functions as a temporary
reservoir for urine

17. Kidneys and their structures
Nephron
 Most basic microscopic
structures of the kidneys
 Inside each kidney, there
are about 1 million
nephrons
 Physiological unit of the
kidney used for filtration
of blood, and reabsorption
and secretion of materials

18. The Nephron
Simplified view of its functions
 Glomerular
Filtration
 Tubular
Reabsorption
 Tubular
Secretion
 Excretion

19. The Nephron
Locations for filtration, reabsorption,
secretion & excretion

20. The Kidney Nephron Diagram

21. Nephron structures and functions
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

22. Nephron structures and functions
 Glomerulus
 The site for blood filtration
 operates as a nonspecific filter -
removes both useful and non-useful
material
 the product of the glomerulus – filtrate
 Bowman’s Capsule
 A sac that encloses glomerulus
 transfers filtrate from the glomerulus
to the Proximal Convoluted Tubule
(PCT)

23. Nephron structures and functions
Proximal Convoluted Tubule (PCT)
 A thick, constantly active segment of the nephron
 that reabsorbs most of the useful substances of the
filtrate: sodium (65%), water (65%), bicarbonate
(90%), chloride (50%), glucose (nearly 100%)
 The primary site for secretion (elimination) of
drugs, waste and hydrogen ions.

24. Nephron structures and functions
 The loop of Henle
 U-shaped tube that consists of a
descending limb and an
ascending limb.
 begins in the cortex, receiving
filtrate from the PCT, extends
into the medulla, and then
returns to the cortex to empty
into the distal convoluted
tubule(DCT).
 Its primary role is to concentrate
the salt in the interstitium, the
tissue surrounding the loop.

25. Nephron structures and functions
Decending Limb of the Loop of Henle
 A part of the counter current multiplier
 fully permeable to water and completely impermeable to
solutes (salt particles)
 receives filtrate from the PCT, allows water to be
absorbed and passes “salty” filtrate to the next segment.
“Saves water and passes the salt”

26. Nephron structures and functions
Ascending Limb of the loop of Henle
 a part of the counter current multiplier
 impermeable to water and actively transports (reabsorbs)
salt (NaCl) to the interstitial fluid of the pyramids in the
medulla.
“Saves salt and passes the water.”
 the passing filtrate becomes dilute and the interstitium
becomes hyperosmotic

27. Nephron structures and functions
Distal Convoluted Tubule (DCT)
 Variably active
portion of the
Nephron
 receives dilute
fluid from
the ascending
limb of the loop
of Henle

28. Nephron structures and functions
Collecting Duct
 variably active portion of
the Nephron
 receives fluid from the
DCT
 The last segment to save
water for the body

29. Nephron structures and functions
Peritubular
Capillaries
 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

30. PHYSIOLOGY

31. I am happy that
now you know
more about me!!!

32. Questions?

33. Kidney nephron
The nephrons are the functional units of the
kidney and are the site of:
1. Filtration of blood
2. Maintainance of Renal blood pressure
3. Formation of urine
4. Counter current mechanism
5. Acid-base balance
6. Regulation of electrolytes
7. Reabsorption of materials
8. Secretion of materials( production of hormones)
9. Excretion of wastes

34. 1. Filtration of Blood
The glomerulus is the site of filtration of blood

35. The Bowman’s capsule (basement membrane +
podocytes)
 filters blood,
 hold back large molecules such as proteins,
 passes through small molecules such as water,
salts, and sugar
 Aids in the formation of urine

37. Podocytes:
• Also known as visceral epithelial cells
• Cells in the Bowman's capsule in the kidneys that wrap
around the capillaries of the glomerulus leaving slits
between them.
• They are involved in regulation of glomerular filtration
rate (GFR). When podocytes contract, they cause
closure of filtration slits. This decreases the GFR by
reducing the surface area available for filtration.

38. 2. Maintainance of Renal Blood
Pressure
• This process is achieved by the
Juxtaglomerular apparatus.

39. The three cellular components of the
apparatus are the
1. juxtaglomerular cells
2. macula densa,
3. extraglomerular mesangial cells .

40. The Juxtaglomerular Apparatus

41. Function of the JC cells
1. Release of Renin
Stimulus : Low blood pressure
Action : Release of Renin
Angiotensin Angiotensin I Angiotensin II
Angiotensin II
 It acts as a vasoconstrictor to raise blood pressure.
 It stimulates the release of aldosterone hormone from the
adrenal cortex.

42. 2. Release of Aldosterone hormone
 It stimulates the DCT to reabsorb salt.
3. Reabsorption of salt (NaCl)
 Salt reabsorption induces the
movement of water to the blood
by osmosis thereby raising the
blood volume and hence
increasing the blood pressure.

43. Function of the Macula Densa Cells
 It monitors the salt content of the blood.
 If concentration of salt is raised, the macula densa cells
inhibit the release of renin from the JC cells.
 No release of renin No angiotensin II , No
aldosterone . Blood pressure decreases until it is sent
back to normal.

44. Function of the extra glomerular
mesangial cells
 It secretes erythropoietin
 Erythropoietin is a glycoprotein hormone which
controls erythropoiesis or red blood cell
production.

45. 3. Formation of urine
 Takes place in 3 main steps;
1. Ultrafiltration
◦ seeping of fluid from glomerular capillaries to the
Bowman’s capsule along with useful substances (e.g.
glucose, vitamins ,amino acids)
2. Reabsorption along the nephron
◦ PCT; selective reabsorption of useful substances
◦ LOH, DCT and CD Reabsorption of water and salts
3. Secretion from blood to tubule

46. 4.Counter Current Multiplier
 Down the descending limb of the LOH, fluid becomes
more concentrated due to loss of water.
 Na+ and Cl- concentration increase as fluid turns and
heads on towards the ascending limb.
 All the way up osmotic pressure of fluid in LOH is
almost equal to the osmotic pressure in interstitial fluid.
 The fluid again passes through hypertonic interstitial
fluid loosing water again until into the collecting duct.
 The final product in the CD is urine!!!!

47. Counter current Multiplier
Interstitial fluid should
be hypertonic for water
to be reabsorbed

48. 5. Regulation of electrolyte
Electrolytes are substances that become ions in solution and
acquire the capacity to conduct electricity.
The primary ions of electrolytes are sodium (Na+), potassium(K+),
calcium (Ca2+), magnesium (Mg2+), chloride (Cl−), hydrogen
phosphate (HPO4
2−), and hydrogen carbonate (HCO3
−).
 Maintenance of an electrolyte balance occurs so that the
osmolarity of both the body fluids and the urine is the same.
 Maximum electrolyte balance is maintained by the release of
hormones which are going to trigger the reabsorption of certain
ions thereby preventing electrolyte disbalances.

49. ADH
 Also known as vasopressin
 Released by hypothalamus
Stimulus: Low blood level
 Prevents the production of dilute urine
 Helps in reabsorption of water in kidneys
 Maintains osmolarity of plasma levels
normal

50. 6. Acid-base balance
 Forms part of human homeostasis
 Is important to maintain cellular stability
 Alterations in the acid-base balance are resisted by
extracellular and intracellular chemical buffers and by
respiratory and renal regulation.
In acid-base balance, the kidney is responsible
for 2 major activities:
◦ Reabsorption of filtered bicarbonate: 4,000 to 5,000 mmol/day
◦ Excretion of the fixed acids (acid anion and associated H+): about 1
mmol/kg/day.

51. Formation of H+
 Secretion from the organic acid and base secretory system
(uric acid, antibiotics and diuretics).
 H2CO3 H+ + HCO3
-
In case of high H+
 H+ is bound to ammonia, phosphate and bicarbonate to
form NH4
+, H2PO4
-, CO2 and H2O.

52. 7. Reabsorption of
materials
Nutrients such as glucose, amino acids
and other metabolites are reabsorbed in
the medulla such that the body does not
lose important nutrients.
Location: proximal convoluted tubule
situated in the cortex of the kidney

53. 8. Secretion of substances
Release of several substances occur in
order to aid in the functions of the kidney:
1. Calcitriol (activated form of vitamin D promotes intestinal
absorption of calcium and the renal reabsorption of phosphate)
2. Renin
3. Erythropoietin
4. ADH
5. Prostaglandins
6. Kinins
7. 1,25-dihydroxyvitamin D3

54. 9. Excretion of wastes
The kidney is also involved in the excretion
of wastes such as:
1. Urea ( from protein metabolism)
2. Uric acid ( from nucleic acid metabolism)
3. Creatinine (from metabolic breakdown of
creatine phosphate)
4. End-products of Hb metabolism
5. Metabolites of hormones
6. Foreign substances: drugs, pesticides,
other chemicals ingested in food

55. Finding the amount of a substance
excreted per unit time
Given
 Amount filtered in NaCl g/day
 Amount reabsorbed in NaCl g/day
 Amount excreted in NaCl g/day
Amount excreted =
Amount filtered – Amount reabsorbed

56. Plasma clearance rate
It is defined of the amount of blood cleaned of a
substance per unit time.
Clearance is a function of glomerular filtration,
secretion from the peritubular capillaries to the
nephron, and reabsorption from the nephron back
to the peritubular capillaries.

57. Finding plasma clearance rate
C = V x U/P
C = plasma clearance rate in ml/min
V =urine production rate in ml/min
U= concentration of a substance in urine in mg/ml
P= concentration of a substance in plasma in mg/ml
Units of plasma clearance rate: ml/min

58. I am happy that
now you know
more about me!!!

59. Questions?

60. 4.Counter Current Multiplier
 A system of limbs
running in opposite
directions
 Consists of;
Descending limb and
Ascending limb of the
Loop of Henle.
 Helps in the absorption
of water from fluid
found in the LOH

61. Counter current multipier
 Down the descending limb of the LOH, fluid becomes
more concentrated due to loss of water.
 Na+ and Cl- concentration increase as fluid turns and
heads on towards the ascending limb.
 All the way up osmotic pressure of fluid in LOH is
almost equal to the osmotic pressure in interstitial fluid.
 The fluid again passes through hypertonic interstitial
fluid loosing water again until into the collecting duct.
 The final product in the CD is urine!!!!

65. Kidney disorders
 Are diseases that affect the kidney.
 Usually affects both kidneys.
 The kidneys ability to remove waste
products and control water balance is
severely affected.
 This causes an accumulation of waste
products and fluids causing severe uremia.
 Uremia=kidney failure

67. There is a rich blood supply
surrounding each nephron, which is
important for the reabsorption
process. The cubical epithelial cells
lining the tubule invaginates to form
intercellular and subcellular spaces
next to the basement membrane of
the capillaries. Glucose and amino
acids are absorbed into the blood by
active transport across the infolded
membranes and subcellular spaces.
These solutes diffuse from the filtrate
into the cells, then through to the
subcellular spaces and then into the
bloodstream. This sets up a

68. Other mineral ions are also actively reabsorbed the way
glucose and amino acids are. As so many of the solutes are
removed, the filtrate becomes hypotonic (lower
concentration of solute molecules) than the surrounding
blood, stimulating water to move via osmosis from the
filtrate to the blood. This leads to the filtrate and the blood
being isotonic (same solute concentrations) by the time the
filtrate reaches the end of the tubule. However, since urea
is not actively reabsorbed, its concentration in the filtrate is
much higher than in the blood and some of the urea
unavoidably diffuses back into the bloodstream and is
taken away.

70. THE LOOP OF HENLE
This hairpin-bend structure has a descending
limb and an ascending limb and is found in the
medulla of the kidney. The descending limb has
thin walls permeable to water and penetrates deep
into the medulla but the ascending limb has
thicker, relatively impermeable walls that returns
to the cortex. Surrounding the loop is a network
of capillaries, one part of which has the same
hairpin structure and is called the vasa recta.

71. Urine formation:
 Filtration from of plasma
from the glomerular
capillaries into the
Bowman’s space.
 Movement from the
tubular lumen to the
peritubular capillaries is
the process called
tubular reabsorption
 Movement from the
peritubular capillaries to
the tubular lumen is the
process known as
tubular secretion
BASIC RENAL PROCESS

72.  Once in the tubule the
substance need not
be excreted , it can
be reabsorbed.
 These processes do
not apply to all
substances. E.g.
- Glucose (completely
reabsorbed.)
- Toxins ( Secreted and
not reabsorbed)

73. Metabolism by Tubules
The cells of the renal tubules
synthesize glucose and add it to the
blood.
Cells also catabolize substances such
as peptides which are taken from the
tubular lumen or peritubular
capillaries.
Catabolism eliminates these
substances from the body.

74. OSMOLARITY:
Osmolarity is the measure of solute concentration, defined
as the number of osmoles (Osm) of solute per liter (L) of
solution(osmol/L or Osm/L).
NOTE: Molarity measures the number of moles solute per
unit volume of solution,

75. Counter current multiplier
Na+ is actively pumped out
of the ascending limb into the
interstitial fluid.
 Cl- follows Na+ passively
 Increases the Na+ and Cl-
of interstitial fluid by about
4 times.
 Water seeps out of the of
the descending limb into
the interstitial fluid by
osmosis

76. The two types of Nephrons
Cortical
• The loop of Henle does
not extend past the
cortex of the kidney.
Juxtamedullary
• Loop of Henle extends
past the cortex and into
the medulla of the
kidney.