anatomy and physiology of renal system

1. Renal System
Deependra Shrestha
MSc Clinical Biochemistry
Second Year
2074

2. Kidney Overview
• The urinary system consists of two kidneys, two
ureters, one urinary bladder, and one urethra
• After the kidneys filter blood plasma, they return most
of the water and solutes back to the bloodstream.
• The remaining water and solutes constitute urine,
which passes through the ureters and is stored in the
urinary bladder until it is excreted from the body
through the urethra.
• Humans produce about 1.5 liters of urine over 24
hours, although this amount may vary according to
circumstances.
• The renal arteries deliver 20–25% of the resting cardiac
output to the kidneys.

3. Functions overview
• Regulation of blood ionic composition
• Regulation of blood pH
• Regulation of blood volume
• Regulation of blood pressure
• Maintenance of blood osmolarity
• Production of hormone
• Regulation of blood glucose level
• Excretion of waste and foreign substance

4. Anatomy
• Bean shaped reddish brown paired organ.
• Rectroperitoneal and located on T11 to L3
• Right kidney is slightly lower than the left.
• Adult kidney is about 12 cm long and weight 150 g
• Concave part of kidney is helium through which
ureter, blood vessels, lymphatics and nerves
emerges.
• Kidney is surrounded by three layer- Renal Fascia,
Adipose Tissue, and Renal Capsule.

5. • Internal anatomy contain two distinct region
• Renal Cortex- Superficial light red area
• Renal Medulla- Deep inner region
• The medulla is divided into multiple cone-shaped
masses of tissue called renal pyramids.
• The base of each pyramid originates at the border
between the cortex and medulla and terminates in
the papilla.
• Papila projects into the space of the renal pelvis
through minor calyx(8-18) and major calyx(2-3)
• Ureter extend from renal pelvis to urinary bladder.

6. Blood supply

7. Nephron
• The functional unit of kidney is called
nephron
• Each kidney has been reported to contain
between 600,000 to 1.5 million nephron.
• Nephron consist of a glomerulus, proximal
tubules, Loop of Henle, distal tubule and
collecting ducts
• The collecting ducts ultimately combine to
develop into renal calyx where urine collects
before passing along ureter and into the
bladder.

8. Glomerulus

9. Glomerular capillaries

10. Glomerular Capillaries
• Glomerular endothelial cell is 40 nm thick and has a
pore of 60 nm diameter.
• The pore constitute 20 to 50 % of glomerular
endothelial surface.
• Cells surface of endothelial layer consist of
negatively charge glycoprotein, proteoglycan,
heparan sulfate which form charge barrier to the
negatively charged protein molecules
• The endothelium permits virtually free access of
plasma and small solutes to the basement
membrane.

11. • The basement membrane is much thicker at about
400 nm and consist of three layer
• Lamina rara interna
• Lamina densa
• Lamina rara externa
• Basement membrane consist of collagen fibrils and
negative charged polyionic glycoprotein such as
heparan sulfate.
• These membrane also serve as charge
discrimination to passage for protein

12. • Podocytes are the epithelial cell lining outside of the
glomerular capillaries.
• These cells have octopus like structure in that they have
a large number of cytoplasmic extension or foot
processes that embedded in the basement membrane.
• Podocytes consist of nephrin which is crucial for the
maintenance of larger protein within the circulation.
• Podocytes consist of glycocalyx of sulfated molecules,
including glycosaminoglycan and glycoconjugates (e.g.
podocalyxin)

13. • Mesangial cells are found between and within the
capillary loops and suspended in the matrix
• Mesangial cells have the characteristic of smooth
muscle cells which are rich in microfilament.
• It responds to the various stimuli such as
• Angiotensin II
• Antidiuretic hormone ADH or vasopressin
• It helps in regulation of GFR.

14. • Proximal tubules is the most metabolically active part
of the nephron
• 15mm long, consist of millions of microvilli, which
expand the surface area for absorption of tubular fluid
• Loop of Henle- hair pin like structure, consist of
cuboidal of columnar cell without brushborder.
• The main role of loop of henle is to assist in generating
concentrated urine, hypertonic with respect to plasma
• Distal convoluted tubules- cells are tall and cuboidal
• Na,K ATPase activity is higher in this region
• Reasorption of Na and Cl, with passive reabsorption of
water

15. • Collecting duct- they are formed form collection of
approx. six distal tubules
• Two main type of cells are found
• Principle cells
• Intercalated cells
• Intercalated cells have high activity of carbonic
anhydrase but no NaK ATPase activity.

16. Juxtaglomerular Apparatus
• In each nephron, the final part of the ascending limb of the
loop of Henle makes contact with the afferent arteriole
serving that renal corpuscle.
• Because the columnar tubule cells in this region are
crowded together to form macula densa.
• Alongside the macula densa, the wall of the afferent
arteriole contains modified smooth muscle fibers called
juxtaglomerular (JG) cells.
• Together with the macula densa, they constitute the
juxtaglomerular apparatus (JGA)
• It plays an important in maintaining systemic blood pressure
through regulation of the circulating intravascular blood
volume and sodium concentration via the renin-angiotensin
aldosterone system (RAAS).

17. Renin-Angiotensin Aldosterone
system (RAAS).
• Angiotensin II affects renal physiology in
three main ways
1. It decreases the glomerular filtration rate
by causing vasoconstriction of the
afferent arterioles.
2. It enhances reabsorption of Na, Cl, and
water in the proximal convoluted tubule
by stimulating the activity of Na/H
antiporters.
3. It stimulates the adrenal cortex to release
aldosterone, a hormone that in turn
stimulates the principal cells in the
collecting ducts to reabsorb more Na and
Cl and secrete more K. The osmotic
consequence of reabsorbing more Na and
Cl is that more water is reabsorbed, which
causes an increase in blood volume and
blood pressure.

18. Net filtration pressure
• Glomerular filtration
depends on three main
pressure
• One pressure promotes
filtration
• Glomerular blood hydrostatic
pressure
• Two pressure oppose
filtration
• Capsular hydrostatic pressure
• Blood colloid osmotic pressure

20. Glomerular filtration rate
• The amount of filtrate formed in all the renal
corpuscles of both kidney each minute is the
glomerular filtration rate(GFR).
• If the GFR is too high, needed substance may pass so
quickly through the renal tubules that some are not
reabsorbed and are lost in the urine
• If the GFR is to low nearly all the filtrate may be
reabsorbed and certain waste product may not be
adequately excreted
• GFR is directly related to the pressure that determine
net filtration pressure; any change in net filtration
pressure will affect GFR.

21. †In addition to being filtered and reabsorbed, urea is secreted.
‡After virtually all filtered K is reabsorbed in the convoluted tubules and loop of Henle, a
variable amount of K is secreted by principal cells in the collecting duct

22. Reabsorption route and transport
mechanism

23. Transport mechanism
• Diffusion
• Active transport
• Primary active transport
• Sodium potassium pump
• Secondary active transport
• Symporters and antiporters
• Obligatory water reabsorption
• Facultative water reabsorption

24. Tubular secretion
• Transfer of material from the blood and tubule cells
into glomerular filtrate is called tubular secretion
• Secreted substance includes
• Hydrogen ion
• Ammonium ion
• Creatinine
• Certain drugs such as penicillin
• It has two important outcome
• Secretion of H+ helps to maintain blood pH
• Secretion of other substance helps to eliminate them
from the body

25. Tubular reabsorption
• The return of most of the filtered water and many
of the filtered solute to the blood stream in called
tubular reabsorption.
• It is the second basic function of the nephron and
collecting duct
• Normally 99% of the filtered water is reabsorbed by
nephron.
• Epithelial cells all along the renal tubules and duct
carry out reabsorption
• PCT makes largest contribution

26. • Solutes that are reabsorbed by both active and
passive processes include
• Glucose
• Amino acids
• Urea
• Ions(Na+, K+, Ca2+, Cl-, HCO3
- HPO4
2-
• Once the fluid passed through the PCT fine –tune
of the reabsorption process takes place by the cells
located more distally.
• Most protein and peptide that pass through the
filter also are reabsorbed , usually via pinocytosis.

27. Reabsorption and secretion in the
PCT
• Na is the major solute reabsorbed in the
PCT
• It occurs by symporter and antiporter
protein located on the cell membrane
• Normally, filtered glucose, amino acids,
lactic acid, water-soluble vitamins, and
other nutrients are not lost in the urine.
• Rather, they are completely reabsorbed in
the first half of the proximal convoluted
tubule by several types of Na+ symporters
located in the apical membrane.
• Two Na+ and a molecule of glucose
attached to symporter protein which
carries them from the tubular fluid into the
tubules cells.

28. • Another SAT is Na/H
antiporter
• It filtered Na down its
concentration gradient into
PCT cell as H+ is moved from
cytosol into the lumen
• Causing Na+ reabsorbed into
the blood and H+ secreted
into tubular lumen

29. • Each reabsorbed solute increases the
osmolarity, first inside the tubule cell,
then in interstitial fluid, and finally in the
blood.
• Reabsorption of the solutes creates an
osmotic gradient that promotes the
reabsorption of water via osmosis
• Water thus moves rapidly from the tubular
fluid, via both the paracellular and
transcellular routes, into the peritubular
capillaries and restores osmotic balance.
• Cells lining the proximal convoluted tubule
and the descending limb of the loop of
Henle are especially permeable to water
because they have many molecules of
aquaporin-1.
• This integral protein in the plasma
membrane is a water channel that greatly
increases the rate of water movement
across the apical and basolateral
membranes.

31. Reabsorption in Loop of Henle
• Here, for the first time, reabsorption of water via
osmosis is not automatically coupled to reabsorption
of filtered solutes because part of the loop of Henle is
relatively impermeable to water.
• The apical membranes of cells in the thick ascending
limb of the loop of Henle have Na+–K+–2Cl-
symporters that simultaneously reclaim one Na+, one
K+, and two Cl- from the fluid in the tubular lumen.
• Na+ that is actively transported into interstitial fluid at
the base and sides of the cell diffuses into the vasa
recta.
• Cl- moves through leakage channels in the basolateral
membrane into interstitial fluid and then into the
vasa recta.
• Because many K+ leakage channels are present in the
apical membrane, most K+ brought in by the
symporters moves down its concentration gradient
back into the tubular fluid.
• Thus, the main effect of the Na+–K+–2Cl symporters is
reabsorption of Na+ and Cl-.

32. • The movement of positively charged
K+ into the tubular fluid through the
apical membrane channels leaves the
interstitial fluid and blood with more
negative charges relative to fluid in
the ascending limb of the loop of
Henle.
• This relative negativity promotes
reabsorption of cations—Na+, K+, Ca2+,
and Mg2+—via the paracellular route.
• Although about 15% of the filtered
water is reabsorbed in the descending
limb of the loop of Henle, little or no
water is reabsorbed in the ascending
limb. In this segment of the tubule,
the apical membranes are virtually
impermeable to water.

33. Reabsorption in the Loop of Henle

34. Reabsorption in the early DCT
• Reabsorption of Na+ and Cl- occurs by
means of Na+–Cl- symporters in the
apical membranes.
• Sodium–potassium pumps and Cl-
leakage channels in the basolateral
membranes then permit reabsorption of
Na+ and Cl- into the peritubular
capillaries.
• The early DCT also is a major site where
parathyroid hormone (PTH) stimulates
reabsorption of Ca2+.
• The amount of Ca2+ reabsorption in the
early DCT varies depending on the
body’s needs.

35. Reabsorption and secretion in the
late Distal Convoluted Tubule and
Collecting ducts
• Two types of cells are present
• Principle cells
• Reabsorb Na+ and secrete K+
• Intercalated cells
• Reabsorb K+ and HCO3
- and secrete H+
• Na+ passes through the apical membrane of
principal cells via Na+ leakage channels. This
channel is called Epithelial sodium channel
ENaC
• Basolateral Na/K pump continuously brings
K+ into principle cells and intracellular
concentration of K+ remains high
• K+ leakage channel are present in both the
apical and basolateral membranes.
• Thus K+ diffuse down its concentration
gradient into the tubular fluid, where K+
concentration is very low.

36. Reabsorption and secretion in the
late Distal Convoluted Tubule and
Collecting ducts

39. Thank You