1. College of Medicine & KKUH
RENAL PHYSIOLOGY
DR SYED SHAHID HABIB
MBBS DSDM FCPS
Associate Professor
Dept. of Physiology
College of Medicine & KKUH

2. Glomerular Filtration Tubular Processing Urine Concentrating Mechanism
Renal Physiology
Introduction
Glomerular Filtration
Tubular Processing
Urine Concentrating Mechanism
Micturition

3. RENAL PHYSIOLOGY TUBULAR PROCESSING TUBULAR REABSORPTION & SECRETION

4. Bright Yellow & transparent
URINE COMPOSITION pH
usually acidic (pH 6)
range=
Colour
Bright Yellow & transparent
Volume
1 - 2 L per day
Glucose
None

5. REABSORTION PATHWAYS
Sodium is a substance that moves through both routes, although most of the sodium is transported through the transcellular pathway. In some nephron segments, especially the proximal tubule, water is also reabsorbed across the paracellular pathway, and substances dissolved in the water, especially potassium, magnesium, and chloride ions, are carried with the reabsorbed fluid between the cells.

7. urea
inulin
gluc
Creat
Urinary Excretion Rate = Filtration Rate – Reabsorption Rate + Secretion Rate

8. % of Filtered Load Reabsorbed
% of Filtered Load Reabsorbed
Glucose (g/day)
100
Bicarbonate (mEq/day)
>99.9
Sodium (mEq/day)
99.4
Chloride (mEq/day)
99.1
Potassium (mEq/day)
87.8
Urea (g/day) 50
Creatinine (g/day)
Urea
Glucose
From Table 27-1, two things are immediately apparent. First, the processes of glomerular filtration and tubular reabsorption are quantitatively very large relative to urinary excretion for many substances. This means that a small change in glomerular filtration or tubular reabsorption can potentially cause a relatively large change in urinary excretion. For example, a 10 per cent decrease in tubular reabsorption, from to L/day, would increase urine volume from 1.5 to 19.3 L/day (almost a 13-fold increase) if the glomerular filtration rate (GFR) remained constant. In reality, however, changes in tubular reabsorption and glomerular filtration are closely coordinated, so that large fluctuations in urinary excretion are avoided.

9. PROXIMAL CONVOLUTED TUBULE
many mitochondria
brush border
tight junctions
lateral intercellular spaces.

10. GLUCOSE AND AMINO ACID REABSORPTION IN NEPHRON

11. TUBULAR TRANSPORT MAXIMUM
The Maximum limit/rate at which a solute can be transported across the tubular cells of kidneys is called TUBULAR TRANSPORT MAXIMUM
Tm for Glucose is 375 mg/min

12. GLUCOSE REABSORPTION FBG=60-110 mg/dl RBG=110-200 mg/dl Transport max
375 mg/min
Renal Threshold
200mg/dl
However, when the plasma concentration of glucose rises above about 200 mg/100 ml, increasing the filtered load to about 250 mg/min, a small amount of glucose begins to appear in the urine. This point is termed the threshold for glucose. Note that this appearance of glucose in the urine (at the threshold) occurs before the transport maximum is reached. One reason for the difference between threshold and transport maximum is that not all nephrons have the same transport maximum for glucose, and some of the nephrons excrete glucose before others have reached their transport maximum. The overall transport maximum for the kidneys, which is normally about 375 mg/min, is reached when all nephrons have reached their maximal capacity to reabsorb glucose.

13. Na-H COUNTER TRANSPORT
Luminal Membrane
HYDROGEN
Secreted in Proximal Tubule and LOH by Counter Transport with Na
PCT & LOH

14. PCT G water Reabsoprtion 65% ATP Na Na AA Na Na H+ K Cl- Cotransport
Countertransport
Cl-

15. SODIUM HANDLING
Na+ moves by co transport or exchange from the tubular lumen into tubular epithelial cells
From cells into interstitium it moves by primary active transport
In DCT and CT it is under hormonal control

16. SODIUM HANDLING

17. Renal tubular reabsorption
Solute reaborption in the proximal tubule is isosmotic (water follows solute osmotically and tubular fluid osmolality remains similar to that of plasma).
65% of water and sodium reabsorption occurs in the proximal tubule
100% of glucose & amino acids
Proximal tubules: coarse adjustment
Distal tubules: fine adjustment (hormonal control).

18. THIN LOOP OF HENLE
few mitochondria
flattened with few microvilli

19. THIN DESCENDING LOOP OF HENLE
few mitochondria
flattened with few microvilli
Solutes
H2O

20. THICK ASCENDING LOOP OF HANLE AND EARLY DCT
Many mitochondria and microvilli, but fewer than in the proximal tubule

21. ASCENDING LOOP OF HENLE
Many mitochondria and microvilli, but fewer than in the proximal tubule
Solutes
H2O

22. Events in Thick ALOH ECF Epithelial Cells Lumen
Figure 27-9 Mechanisms of sodium, chloride, and potassium transport in the thick ascending loop of Henle. The sodium-potassium ATPase pump in the basolateral cell membrane maintains a low intracellular sodium concentration and a negative electrical potential in the cell. The 1-sodium, 2-chloride, 1-potassium co-transporter in the luminal membrane transports these three ions from the tubular lumen into the cells, using the potential energy released by diffusion of sodium down an electrochemical gradient into the cells. Sodium is also transported into the tubular cell by sodium-hydrogen counter-transport. The positive charge (+8 mV) of the tubular lumen relative to the interstitial fluid forces cations such as Mg++ and Ca++ to diffuse from the lumen to the interstitial fluid via the paracellular pathway.
Sodium potassium 2 chloride co transport 22

23. Absorption through loop of Henle:
Descending limb: is water permeable and allow absorption of 15% of filtered H2O. It is impermeable to Na-CL.
Thin ascending limb: is impermeable to H2O, but permeable to Na-Cl, where they are absorbed passively in this part .
Thick ascending limb: is impermeable to H2O.
Na-K-2Cl co-transport occur in this part (25% of Na).

24. Na-H COUNTER TRANSPORT
ASCENDING LOOP OF HENLE
Na-H COUNTER TRANSPORT
Luminal Membrane
HYDROGEN
Secreted in Proximal Tubule and LOH by Counter Transport with Na
PCT & LOH

25. LATE DCT AND CORTICAL COLLECTING DUCT
Mitochondria and microvilli decrease.
Principal Cells (Na Abs and ADH related Water abs)
Intercalated Cells (Acid Sec and HCO3 Transport)

26. DCT AND COLLECTING DUCT
I Cell
P Cell
Principal Cells (Water reabsortion)
Intercalated Cells (Acid Secretion)

27. Events in
DCT
Figure Cellular ultrastructure and transport characteristics of the early distal tubule and the late distal tubule and collecting tubule. The early distal tubule has many of the same characteristics as the thick ascending loop of Henle and reabsorbs sodium, chloride, calcium, and magnesium but is virtually impermeable to water and urea. The late distal tubules and cortical collecting tubules are composed of two distinct cell types, the principal cells and the intercalated cells. The principal cells reabsorb sodium from the lumen and secrete potassium ions into the lumen. The intercalated cells reabsorb potassium and bicarbonate ions from the lumen and secrete hydrogen ions into the lumen. The reabsorption of water from this tubular segment is controlled by the concentration of antidiuretic hormone

28. Intercalated cell
Events in
DCT & CT

29. Events in
DCT & CT
Aldosterone
Principal Cell

30. Distal convoluted tubule and collecting ducts
What happens here depends on hormonal control:
Aldosterone affects Na+ and K+
ADH – facultative water reabsorption

31. FACTORS AFFECTING ADH Increase ADH Decrease ADH ↑Osmolarity
↓ Blood volume
↑ Blood volume
↓ Blood pressure
↑ Blood pressure

32. Clinical applications
Thiazide diuretics
Loop diuretics:
K+ sparring diuretics:

33. MEDULLARY COLLECTING DUCT

34. REABSORPTION OF WATER IN DIFFERENT SEGMENTS OF TUBULES
PART OF NEPHRON
PERCENTAGE
REABSORBED
Proximal tubules 65
Loop of Henle 15
Distal tubules 10
Collecting ducts
9.2
Passing into urine
0.8

35. RENAL PHYSIOLOGY TUBULAR SECRETION
DR SYED SHAHID HABIB
MBBS, FCPS

36. TUBULAR SECRETION
Tubular Secretion may be by Passive or Active Mechanisms
The most important secretory processes are for H, K and Organic Ions

37. HYDROGEN Secreted in Proximal Tubule by Counter Transport with Na
In DCT and CT it is secreted by Hydrogen ATP ase
When body fluids are more acidic H secretory process is accelerated and Vice Versa

38. Na-H COUNTER TRANSPORT
Luminal Membrane
HYDROGEN
Secreted in Proximal Tubule and LOH by Counter Transport with Na
Secreted in DCT by H ATP ase Primary Active Transport
PCT & LOH
I Cell in DCT

39. RENAL PHYSIOLOGY COUNTER CURRENT MECHANISM

40. COUNTER CURRENT MECHANISM
KIDNEYS HAVE
MECHANISMS FOR EXCRETING EXCESS WATER
MECHANISMS FOR EXCRETING EXCESS SOLUTES
Requirements for Excreting a Concentrated Urine-High ADH Levels and Hyperosmotic Renal Medulla

41. NEPHRON TYPES Superficial (cortical) [85 %]
Capable of forming dilute urine
Juxtamedullary [15 %]
Capable of forming concentrated
(> 300 mOsm/kg) urine

42. At least 600 mmol of solutes must be excreted each day
EXCRETION LIMITS
At least 600 mmol of solutes must be excreted each day
minimum volume = 600/1200 = 0.5L
maximum volume = 20 Liters

43. EXCRETION LIMITS

44. COUNTER CURRENT MECHANISM
LOOPS OF HENLE OF JUXTA MEDULLARY NEPHRONS establish hyperosmolality of interstitium of medulla. They are called COUNTER CURRENT MULTIPLIERS
VASA RECTA maintain hyperosmolality established by counter current multipliers. They are called COUNTER CURRENT EXCHANGERS

47. 300
300
200
300
300
Cortex
300
300
250
400
400
300
300
Medulla
500
500
400
600
600
500
400
700
700
600
Osmolality
800
800
800
1000
1000
1000
1200
1200
1200

48. DISORDERS OF URINARY CONCENTRATING ABILITY
Failure to Produce ADH: "Central" Diabetes Insipidus.
Inability of the Kidneys to Respond to ADH: "Nephrogenic"
Diabetes Insipidus.

49. RENAL PHYSIOLOGY MICTURITION
DR SYED SHAHID HABIB
MBBS DSDM FCPS
Assistant Professor
Dept. of Physiology
College of Medicine & KKUH

50. MICTURITION
It is the process by which the urinary bladder empties when it becomes filled
Filling of bladder.
Micturition reflex.
Voluntary control.

51. Physiologic Anatomy and Nervous Connections of the Bladder
Composed of
Body
Neck……..post urethra (stretch receptors)
External sphincter.
Pelvic diaphragm.
A reservoir … adult … ml
DETRUSOR MUSCLE … pr can rise upto mmHg.
Mucosa… RUGAE …TRIGONE

52. Nervous Connections of the Bladder
Urogenital diaphragm

53. Micturition Reflex
Actions of the internal urethral sphincter and the external urethral sphincter are regulated by reflex control center located in the spinal cord.
Filling of the urinary bladder activates the stretch receptors, that send impulses to the micturition center.
Activates parasympathetic neurons, causing rhythmic contraction of the detrusor muscle and relaxation of the internal urethral sphincter.
Voluntary control over the external urethral sphincter.
When urination occurs, descending motor tracts to the micturition center inhibit somatic motor fibers of the external urethral sphincter.
AUTONOMIC SPINAL REFLEX

54. 1 2 3 INNERVATION OF THE BLADDER Nerves Characteristic Function
Pelvic nerves (parasympathetic fibers)
S-2 and S-3
Both sensory and motor nerve fibers
Contraction of bladder
The sensory fibers detect the degree of stretch in the bladder wall 2
Pudendal Nerve
somatic nerve
Fibers that innervate and control the voluntary skeletal muscle of the sphincter 3
Hypogastric Nerves
sympathetic innervation (L2)
Stimulate mainly the blood vessels and have little to do with bladder contraction. Sensory nerve fibers of the sympathetic nerves also mediate the sensation of fullness and pain.

55. CYSTOMETROGRAM