Urine Formation physiology as per modern medical physiological principles.

1. Urine Formation
Dr. Aniket Shilwant
BAMS. MD (Ayurveda Physiology)

2. Introduction to Urine Formation
▪ Blood cleansing function.
▪ Kidney Blood Supply - 1,300 mL of blood (26% of CO)
▪ Normal urine output is 1 L/day to 1.5 L/day.
Processes of Urine Formation
▪ Ultrafiltration
▪ Selective Reabsorption
▪ Tubular Secretion

3. Processes of Urine Formation
Glomerular Filtration
With the desired blood flow to kidneys out of total cardiac output, the plasma is
filtered into Bowman capsule while the blood passes through Glomerular capillaries. This
process is called Glomerular Filtration.
Selective Reabsorption
Glomerular filtrate filtered from Bowman capsule passes through narrow tubule of
Nephron wherein it undergoes various qualitative and quantitative changes. Absorption of
selective substances is carried out thereby and this process is called Tubular reabsorption
or Selective Reabsorption.
Tubular Secretion
Secretion or release of some unwanted substances into the tubule from peritubular
blood vessels is called Tubular Secretion or Excretion.

4. Glomerular Ultrafiltration
Filtration Membrane
Filtration membrane is formed by three layers:
1. Glomerular capillary membrane
2. Basement membrane
3. Visceral layer of Bowman capsule.

5. Glomerular Ultrafiltration
Glomerular capillary membrane
▪ Single layer of endothelial cells, attached to basement membrane.
▪ Capillary membrane - Fenestrae or Filtration pores
Basement membrane
▪ Basement membrane of glomerular capillaries and
basement membrane of visceral layer of Bowman capsule fuse together.
Visceral layer of Bowman capsule
▪ Single layer of flattened epithelial cells (Podocytes) resting on a basement membrane.
▪ Cell – Basement membrane connections - Cytoplasmic extensions - Pedicles or feet.
▪ Small cleft like spaces in between Pedicles – Slit pore or Filtration slit.

6. Glomerular Ultrafiltration
Process of Glomerular Filtration
▪ All the substances of plasma are filtered except the plasma proteins.
▪ The filtered fluid is called glomerular filtrate.
Ultrafiltration
▪ Even the minute particles are filtered.
▪ Plasma proteins are not filtered due to their large molecular size.
▪ No proteins in filtrate and thus in Urine
Normal GFR –
125ml/min OR 180L/day

7. Pressures Determining Filtration
Glomerular Capillary Pressure
▪ It is about 60 mm Hg and, varies between 45 and 70 mm Hg.
Colloidal Osmotic Pressure
▪ Plasma proteins develop the colloidal osmotic pressure, about 25 mm Hg.
Hydrostatic Pressure in Bowman Capsule
▪ It is the pressure exerted by the filtrate in Bowman capsule.
▪ It is also called capsular pressure. It is about 15 mm Hg.
Net Filtration Pressure
▪ Pressure balance between favoring and opposing filtration.
▪ Effective or Essential filtration pressure = 15 to 20mm Hg.

8. Factors affecting GFR
1. Renal Blood Flow
2. Tubuloglomerular Feedback
▪ Conc. of Sodium Chloride increases in the filtrate, GFR increases – Blood flow decreases – GFR
decreases
▪ Conc. of Sodium Chloride decreases in the filtrate, GFR decreases – Blood flow increases – GFR
increases
3. Glomerular Capillary Pressure
4. Colloidal Osmotic Pressure
5. Hydrostatic Pressure in Bowman Capsule
6. Constriction of Afferent Arteriole

9. Factors affecting GFR
7. Constriction of Efferent Arteriole
▪ Initial increase in GFR – Stagnation of blood in G. Capillaries.
▪ Later decrease in GFR – No fresh blood flow
8. Systemic Arterial Pressure
▪ No effect on GFR in MABP
▪ >180mm Hg and < 60mm Hg - Renal blood flow and GFR affected as autoregulatory mechanism
failure.
9. Sympathetic Stimulation
▪ The mild or moderate sympathetic stimulation
▪ Strong sympathetic stimulation - Severe Vasoconstriction – Reduced blood flow later cases

10. Factors affecting GFR
10. Surface Area of Capillary Membrane
11. Permeability of Capillary Membrane
12. Contraction of Glomerular Mesangial Cells
▪ Decreased surface area of capillaries - Reduction in GFR
13. Hormonal and Other Factors
▪ Hormones affect GFR by regulating blood flow either by Vasoconstriction or Vasodilatation

11. Hormones affecting GFR
Sr. No Hormones increasing GFR Hormones decreasing GFR
1 Atrial Natriuretic Peptide – ANP Angiotensin II
2 Brain Natriuretic Peptide – BNP Endothelins
3 Cyclic Adenosine Monophosphate – cAMP Nor-Adrenaline
4 Dopamine Platelet Activating Factor – PAF
5 EDRF – Nitric Oxide Platelet Derived Growth Factor – PDGF
6 Prostaglandin (PGE) Prostaglandin (PGF)

12. ▪ Reabsorption of - Water, Electrolytes, Glucose, Amino acids, Vitamins and other substances
▪ Absorption - Interstitial fluid (Medulla) – Blood (Peritubular capillaries)
▪ Tubular reabsorption – Selective reabsorption
MECHANISM OF REABSORPTION
1. Active reabsorption
2. Passive reabsorption.
Tubular Reabsorption

13. Active Reabsorption
▪ Against the electrochemical (uphill) gradient.
▪ It needs liberation of energy – ATP
▪ Substances reabsorbed actively – Sodium, Calcium, Potassium, Phosphates, Sulfates, Bicarbonates,
Glucose, Amino Acids, Ascorbic Acid, Uric acid and Ketone bodies.
Passive Reabsorption
▪ Along the electrochemical (downhill) gradient. Does not need energy.
▪ Substances reabsorbed passively – Chloride, Urea and Water.
ROUTES OF REABSORPTION
Reabsorption of substances from tubular lumen into the peritubular capillary –
1. Trans-celluar route 2. Paracellular route.
Tubular Reabsorption

14. Tubular Reabsorption
1. Transcellular Route
▪ Substances move through the cell.
a. Tubular lumen into tubular cell through apical
(luminal) surface of the cell membrane
b. Tubular cell into interstitial fluid
c. Interstitial fluid into capillary.
2. Paracelluar Route
▪ Substances move through the intercellular space.
a. Tubular lumen into interstitial fluid of lateral intercellular space between the cells
b. Interstitial fluid into capillary

15. Tubular Reabsorption
SITE OF REABSORPTION
Reabsorption of the substances occurs in almost all the segments of tubular portion of nephron.
1. Substances Reabsorbed from Proximal Convoluted Tubule
▪ Maximum reabsorption from PCT about 7/8 of the filtrate (88%)
▪ Brush border epithelial cells increases the surface area and facilitates reabsorption.
▪ Substances reabsorbed - Glucose, Amino Acids, Sodium, Potassium, Calcium,
Bicarbonates, Chlorides, Phosphates, Urea, Uric acid and Water.
2. Substances Reabsorbed from Loop of Henle
▪ Substances reabsorbed - Sodium and Chloride
3. Substances Reabsorbed from Distal Convoluted Tubule
▪ Substances reabsorbed - Sodium, Calcium, Bicarbonate and Water

16. Tubular Reabsorption
REGULATION OF TUBULAR REABSORBTION
1. Glomerulo-Tubular Balance
▪ Glomerulotubular balance is the balance between the filtration and reabsorption of solutes and
water in kidney.
▪ GFR increase - Tubular load of solutes, water in PCT increases – increase reabsorption
Mechanism of Glomerulo-Tubular Balance
▪ Osmotic pressure in the peritubular capillaries.
▪ GFR increases – accumulation of plasma proteins in glomerulus.
▪ Increased osmotic pressure in the blood – Increased reabsorption of sodium and water

17. Tubular Reabsorption
REGULATION OF TUBULAR REABSORBTION
2. Nervous Factor
▪ Activated sympathetic nervous system - increased tubular reabsorption
▪ Stimulating secretion of renin from JG Cells
▪ Renin – Angiotensin II – Aldosterone – Sodium retention & reabsorption
3. Hormonal Factors
▪ Hormones regulate GFR mentioned in Table.

18. Tubular Reabsorption
Sr.
No
Hormone Action
1 Aldosterone Incr. Sodium reabsorption – Ascending limb, DCT, Collecting Duct
2 Angiotensin II Incr. Sodium reabsorption – PCT, Ascending limb, DCT, Collecting Duct
3 Antidiuretic Hormone (ADH) Incr. Water reabsorption – DCT, Collecting Duct
4 Atrial Natriuretic Peptide (ANP) Decr. Sodium reabsorption
5 Brain Natriuretic Peptide (BNP) Decr. Sodium reabsorption
6
Parathormone (PTH) Incr. reabsorption – Calcium, Magnesium, Hydrogen
Decr. reabsorption – Phosphate
7 Calcitonin Decr. Calcium reabsorption

19. Tubular Reabsorption
1. High-threshold Substances
▪ Substances which do not appear in urine under normal conditions.
▪ Glucose, Amino acids, Acetoacetate ions and Vitamins
▪ These substances appear in urine, only if their concentration in plasma is abnormally high
or in renal failure diseases where reabsorption is affected.
2. Low-threshold Substances
▪ Substances which appear in urine even under normal conditions.
▪ Urea, Uric acid and Phosphate
3. Non-threshold Substances
▪ Substances - not at all reabsorbed and are excreted in urine irrespective of their plasma level.
▪ The metabolic end products – Creatinine

20. Tubular Reabsorption
Reabsorption of Sodium
▪ 99% of sodium is reabsorbed. 2/3rd – PCT & 1/3rd other segments
1. Transport from Lumen of Renal Tubules into the Tubular Epithelial Cells
▪ Active reabsorption of sodium ions from lumen into the tubular cells
▪ Sodium – Hydrogen Antiport pump – PCT
▪ Sodium – Co-Transport mechanism with Glucose & Amino acids.
2. Transport from Tubular Cells into the Interstitial Fluid
▪ Sodium is pumped outside the cells by Sodium-Potassium pump.
3. Transport from Interstitial Fluid to the Blood
▪ From the interstitial fluid, sodium ions enter the peritubular capillaries by concentration gradient.
▪ Sodium reabsorption - Aldosterone action on DCT

21. Tubular Reabsorption
Reabsorption of Water
▪ Reabsorption of water occurs from – PCT, DCT and Collecting Ducts
▪ Reabsorption of water from PCT – obligatory water reabsorption
▪ Obligatory reabsorption - Secondary (obligatory) to sodium reabsorption.
▪ Sodium reabsorption – Osmosis – Movement of water from Renal tubule
▪ Reabsorption of water from DCT and collecting duct – facultative water reabsorption
▪ Facultative reabsorption – Under the activity of Antidiuretic Hormone (ADH).
▪ Only in presence of ADH – DCT & Collecting ducts become permeable to water*
▪ Mechanism of action of ADH – Stimulating water channels – Aquaporins
▪ ADH – ADH Receptors – Adenyl cyclase – cAMP – Aquaporins – Water reabsorption

22. Tubular Reabsorption
Reabsorption of Glucose
▪ Completely reabsorbed in the proximal convoluted tubule.
▪ By secondary active transport - Sodium cotransport mechanism.
▪ Tubular lumen – Tubular cell – Sodium dependent glucose cotransporter 2 (SGLT2).
▪ Tubular cell – Medullary Interstitium - Glucose transporter 2 (GLUT2).
▪ Renal threshold for glucose is 180 mg/dL
Reabsorption of Amino Acids
▪ Complete reabsorption from – PCT
▪ Sodium Co-Transport mechanism

23. Tubular Reabsorption
Reabsorption of Bicarbonates
▪ Reabsorption mostly in PCT
▪ Form – Sodium Bicarbonate – Dissociation
▪ Sodium – Hydrogen pump
▪ Hydrogen + Bicarbonate = Carbonic acid – Reversible reaction
▪ Again formation of Sodium Bicarbonate

24. Tubular Secretion
Substances secreted -
▪ Para-amino-hippuric acid (PAH)
▪ 5hydroxy-indole-acetic acid (5HIAA)
▪ Amino derivatives
▪ Penicillin

25. Tubular Secretion
Substances secreted at different segments of renal tubule
▪ Potassium – Active Transport – Na-K pump – PCT, DCT, Collecting Ducts
▪ Ammonia – PCT
▪ Hydrogen ions (H+) – PCT & DCT
▪ Urea - Loop of Henle

26. Resources
▪ Textbook of Medical Physiology – Guyton & Hall
▪ Ganong’s review of Medical Physiology
▪ Essentials of Medical Physiology – Sembulingam
▪ Images – Internet

27. Dr. Aniket A. Shilwant
Associate Professor, Sharir Kriya Dept.
GJPIASR, CVM University, New Vidyanagar, Anand
ayuraniket18@gmail.com
Thank You All !!!