1. Physiology of kidney and excretion
Romana Šlamberová, MD PhD
Department of Normal, Pathological and Clinical Physiology

2. Urinary system Organ system that produces, stores, and carries urine
Includes two kidneys, two ureters, the urinary bladder, two sphincter muscles, and the urethra.
Humans produce about 1.5 liters of urine over 24 hours, although this amount may vary according to the circumstances.
Increased fluid intake generally increases urine production.
Increased perspiration and respiration may decrease the amount of fluid excreted through the kidneys.
Some medications interfere directly or indirectly with urine production, such as diuretics.

3. Function of urinary system
Excretion
Keeping homeostasis
Keeping acid-base balance
Secretion (rennin, kallikrein, erytropoetin)
Excreted products:
Product of the metabolism
Water
Hormones
Vitamins
Toxic substances

4. Anatomy of urinary system

5. Kidneys
Morphology
It is paired organ (weight about 300 g)
Compound from two parts cortex (isotonic urine) and medulla (hypertonic urine)
Cortex: Glomerular apparatus
Medulla: Divided: Outer and Inner
Consists of about 1 million filtering units termed nephrons (basic structural and functional unit)
The kidney plays a crucial role in regulating electrolytes in the human blood (e.g. Na+, K+, Ca2+).
It clears urea, a nitrogenous waste product from the metabolism of amino acids.

6. Kidney - structure

7. Renal pelvis
The major function of the renal pelvis is to act as a funnel for urine flowing to the ureter.
The renal pelvis represents the funnel-like dilated proximal part of the ureter.
It is the point of convergence of two or three major calices.
Each renal papilla is surrounded by a branch of the renal pelvis called a calyx.

8. Ureters
Urine is collected in the renal pelvis (or pyelum), which connects to the ureters, which carry urine to the bladder.
The ureters are about 200 to 250 mm long.
Smooth muscular tissue in the walls of the ureters peristaltically force the urine downward.

9. Urine flow through ureters
Urine is not flowing through the ureter, but goes to the bladder as an urinary spindle.
Starts with the sucking up of the urine during the diastolic phase → closing of collecting ductus → peristaltic movements.
Small amounts of urine are emptied into the bladder from the ureters about every 10 to 15 seconds.

10. Urinary bladder 1
The urinary bladder is a hollow muscular organ shaped like a balloon.
It is located in the pelvic fossa and held in place by ligaments attached to the pelvic bones.
The bladder stores urine - up to 500 ml of urine comfortably for 2 to 5 hours.
Sphincters (circular muscles) regulate the flow of urine from the bladder.
Internal urethral sphincter = in the beginning of urethra smooth muscle – not under our voluntary control
External urethral sphincter = skeletal muscle – we can control it

11. Urinary bladder 2

12. Urinary bladder 3
The detrusor muscle is a layer of the urinary bladder wall, made up of smooth muscle fibers arranged in inner and outer longitudinal layers and a middle circular layer.
Contraction of the detrusor muscle causes the bladder to expel urine through the urethra.
Problems with this muscle can lead to incontinence.

13. Urethra 1
The urethra has an excretory function in both sexes, to pass urine to the outside, and also a reproductive function in the male, as a passage for sperm.
The external urethral sphincter is a striated smooth muscle that allows voluntary control over urination.
Urethral sphincters:
Internal
External
In males the internal and external urethral sphincters are more powerful, able to retain urine for twice as long as females

14. Urethra 2 Women: shorter
Mans: Longer (together with genital efferent system)
4 parts
Intramuralis
Prostatica
Membranacea
Spongiosa

15. Urination (micturition)
The process of disposing urine from the urinary bladder through the urethra to the outside of the body.
The process of urination is usually under voluntary control.
Urinary incontinence is the inability to control urination, and is more common in women than men.
Urinary retention refers to the inability to urinate.
Enuresis nocturna = incontinence during the night (effects of emotions).

16. Micturition reflex
Activated when the urinary bladder wall is stretched; it results in urination.
This reflex occurs in the spinal cord, specifically in the sacral region that is modified by the higher centers in the brain: the pons and cerebrum.
The presence of urine in the bladder stimulates the stretch receptors, which produces action potential.
The action potentials are carried by sensory neurons to the sacral segments of the spinal cord through the pelvic nerves, the parasympathetic fibers carry the action potentials to the urinary bladder in the pelvic nerves.
The pressure in the urinary bladder increases rapidly once its volume exceeds approximately ml.

17. Nephron 1
A nephron (1-1.2 millions) is the basic structural and functional unit of the kidney.
Its chief function is to regulate water and soluble substances by filtering the blood, reabsorbing what is needed and excreting the rest as urine.
Each nephron is composed of an initial filtering component (the renal corpuscle) and a tubule specialized for reabsorption and excretion (the renal tubule).
The renal corpuscle filters out large solutes from the blood, delivering water and small solutes to the renal tubule for modification.

18. Nephron 2 Parts: Glomerular apparatus Proximal tubule Loop of Henle
Distal tubule
Collecting ducts
Types of nephrons:
Cortical nephrons (glomerular apparatus belong the surface and Loop of Henle only to the outer part of the medulla)
Intermedial nephrons (in the middle)
Juxtamedullary nephrons (glomerular apparatus deep in cortex near the medulla and Loop of Henle is going deep to the inner part of the medulla)

19. Nephron 3

20. Renal (Malphigian) corpuscle
It is the nephron's initial filtering component.
Glomerulus - is a capillary tuft that receives its blood supply from an afferent arteriole and passes into efferent arteriole of the renal circulation.
Efferent arterioles of juxtamedullary nephrons (ie, the 15% of nephrons closest to the medulla) send straight capillary branches that deliver isotonic blood to the renal medulla.
Along with the loop of Henle, these vasa recta play a crucial role in the establishment of the nephron's countercurrent exchange system.
Bowman's capsule - surrounds the glomerulus and is composed of visceral (inner) and parietal (outer) layers.

21. Glomerulus 1

22. Glomerulus 2
The glomerulus has several characteristics that deviate from the features of most other capillaries of the body.
the endothelial cells of the glomerulus contain numerous pores (fenestrae)
glomerular endothelium sits on a very thick basement membrane
On the surface of the cells are negatively charged glycosaminoglycans such as heparan sulfate. The negatively-charged basement membrane repels negatively-charged ions from the blood, helping to prevent their passage into Bowman's space.
blood is carried out of the glomerulus by an efferent arteriole instead of a venule, as is observed in most other capillary systems.

23. Glomerular filter The filtration surface is 1.5 square meter
Amount of the solution, which is filtered in glomerular apparatus is around l.
The rest (97 %) has to be reabsorbed in the tubules back to the body, so the final volume of urine is around ( l per day).
Glomerular filter:
the capillary endothelium
basal membrane
epithelium of the Bowman’s capsule (PODOCYTES)
Podocytes: special cells which have numerous of pseudopodia (pedicles) that interdigitate to form filtration slits along the capillary wall.

24. Glomerular filtration barrier

25. GLOMERULAR FILTRATION
Depends on:
Pressure gradient across the filtration slit (endothelium, basal membrane, epithelium = podocytes)
Blood circulation throughout the kidneys
Permeability of the filtration barrier
Filtration surface
The solution after filtration is very similar like plasma, but should be WITHOUT PROTEINS

26. CLEARANCE
The ability of kidneys to clear plasma from different products.
GLOMERULAR FILTRATION RATE (GFR)
can be measured by measuring the excretion and plasma level of a substance that freely filtered through the glomeruli and neither secreted nor reabsorbed by the tubules, such as INULIN (polymer of fructose).
GFR = U x V/P
U = concentration of inulin in urine
V = volume of the urine
P = concentration of inulin in plasma
Normal GFR is around 125 ml/min (7.5 l/h)

27. Juxtaglomerular apparatus 1
The juxtaglomerular cells are cells that synthesize, store, and secrete the enzyme renin.
Specialized smooth muscle cells in the wall of the afferent arteriole that are in contact with distal tubule.
Have mechano-receptors for blood pressure
The macula densa is an area of closely packed specialized cells lining the distal convoluted tubule where it lies next to the juxtaglomerular apparatus.
Cells of macula densa are taller and have more prominent nuclei than surrounding cells.
Sensitive to the concentration of sodium ions in the fluid.

28. Juxtaglomerular apparatus 2

29. Proximal tubule 1
Morphology: 15 mm long and 55 m in diameter; epithelium cells have a striate brush border (projections), which enlarge the surface for the reabsorption.
Function: Reabsorption of the largest volume of solution filtered in glomerular apparatus.
% water
Na+, Cl-, HCO3-, K+, Ca2+, Mg2+, HPO42-
Glucose
Results in ISOOSMOTIC SOLUTION
Fluid in the filtrate entering the proximal convoluted tubule is reabsorbed into the vasa recta, including approximately 2/3 of the filtered salt and water and all filtered organic solutes (primarily glucose and amino acids).

30. Proximal tubule 2
This is driven by sodium transport from the lumen into the blood by the Na+/K+ ATPase in the basolateral membrane of the epithelial cells.
Much of the mass movement of water and solutes occurs in between the cells through the tight junctions.
The solutes are absorbed isotonically: the osmotic potential of the fluid leaving the proximal tubule is the same as that of the initial glomerular filtrate.
Glucose and amino acids are absorbed actively via cotransport channels driven by the sodium gradient out of the nephron.

31. Lining of tubules
Trojan: Fyziologie

32. Loop of Henle
A U-shaped tube that consists of a descending limb (thin part) and ascending limb (thin and thick part) .
Begins in the cortex, receiving urine from the proximal convoluted tubule, extends into the medulla, and then returns to the cortex to empty into the distal convoluted tubule.
Its primary role is to concentrate the salt in the interstitium, the tissue surrounding the loop.

33. Loop of Henle - Descending limb
Permeable to water and salt, and thus only indirectly contributes to the concentration of the interstitium.
As the filtrate descends deeper into the hypertonic interstitium of the renal medulla, water flows freely out of the descending limb by osmosis until the tonicity of the filtrate and interstitium equilibrate.
Longer descending limbs allow more time for water to flow out of the filtrate, so longer limbs make the filtrate more hypertonic than shorter limbs.
Results in hypertonic solution in tubuli.

34. Water and ion transport

35. Loop of Henle - Ascending limb
Impermeable to water, permeable for salts.
Actively pumps sodium out of the filtrate, generating the hypertonic interstitium that drives countercurrent exchange.
Results in hypotonic solution in tubuli.
This hypotonic filtrate is passed to the distal convoluted tubule in the renal cortex.

36. Distal tubule 1
Morphology: continuation of the thick ascending limb of the Loop of Henle in the cortex of kidneys – direct part.
Convolute part – Juxtaglomerular apparatus (the part of distal tubule near the glomerular apparatus) = special cells = MACULA DENSA (thin cells very tight next to each other) Large nucleus, secretion of RENIN
Reabsorption:
Water
Na+
Results in ISOOSMOTIC SOLUTION
After traveling the length of the distal convoluted tubule, only 3% of water remains, and the remaining salt content is negligible.
97.9% of the water in the glomerular filtrate enters the convoluted tubules and collecting ducts by osmosis.

37. Distal tubule 2
The distal convoluted tubule is similar to the proximal convoluted tubule in structure and function. Cells lining the tubule have numerous mitochondria, enabling active transport to take place by the energy supplied by ATP.
Much of the ion transport taking place in the distal convoluted tubule is regulated by the endocrine system.
In the presence of parathyroid hormone, the distal convoluted tubule reabsorbs more Ca2+ and excretes more phosphate.
When aldosterone is present, more Na+ is reabsorbed and more K+ excreted.
Atrial natriuretic peptide causes the distal convoluted tubule to excrete more Na+ .
In addition, the tubule also secretes hydrogen and ammonium to regulate pH.

38. Water and ion transport

39. Collecting duct 1
Collects about 10 distal tubules, continues as medullary pyramides (about 2700 nephrons).
Final adjustment
Results in HYPERTONIC SOLUTION
Each distal convoluted tubule delivers its filtrate to a collecting duct, most of which begin in the renal cortex and extend deep into the medulla.
As the urine travels down the collecting duct, it passes by the medullary interstitium which has a high sodium concentration as a result of the loop of Henle's.

40. Collecting duct 2
The collecting duct is normally impermeable to water, it becomes permeable under the actions of antidiuretic hormone (ADH).
As much as 3/4 of the water from urine can be reabsorbed as it leaves the collecting duct by osmosis.
The levels of ADH determine whether urine will be concentrated or dilute.
Dehydration results in an increase in ADH, while water sufficiency results in low ADH allowing for diluted urine.

41. Collecting duct 3
Lower portions of the collecting duct are also permeable to urea, allowing some of it to enter the medulla of the kidney, thus maintaining its high ion concentration (which is very important for the nephron).
Urine leaves the collecting duct through the renal papilla, emptying into the renal calyces, the renal pelvis, and finally into the bladder via the ureter.
Because it has a different embryonic origin than the rest of the nephron (the collecting duct is from endoderm whereas the nephron is from mesoderm), the collecting duct is usually not considered a part of the nephron proper.

42. Transportation of the substances 1
Natrium and anorganic substances

43. Transportation of the substances 2
Pasive transport
Simple – only Na+
Co-transport – with Cl-, glucose, aminoacids, phosphates
Anti-transport - Na+ inside, H+ or Ca2+ out
Active transport
Na+/K+- pump – dependent on ATP energy

44. Transportation of the substances 3
Organic substances
Substances which have KIDNEY’S THRESHOLD = like GLUCOSE – physiologically not in urine, when the level of glucose in plasma is higher than the threshold of kidneys reabsorption, than we can se glucose in the urine.
Substances without kidney’s threshold = physiologically in urine
GLUCOSE
Secondary active transport = it is secondary dependent on ATP. It means that glucose transport is together with Na+ as co-transport, and the ATP-dependent natrium-kalium pump helps to keep the gradient of natrium

45. Function - Excretion of waste products
The kidneys excrete a variety of waste products produced by metabolism, for example, urea (from protein catabolism) and uric acid (from nucleic acid metabolism).
UREA
filtered in glomerular apparatus → increase urea concentration in proximal tubule, because of the reabsorption of water → reabsorption of urea later in proximal tubule → back into the Loop of Henle (helps to keep the hypertonic interstitium) → out again in the collecting ductus

46. Function - Homeostasis
Acid-Base Balance
The kidneys regulate the pH, mineral ion concentration, and water composition of the blood.
By exchanging hydronium ions (cation H3O+) and hydroxyl ions (OH), the blood plasma is maintained by the kidney at pH 7.4.
Urine, on the other hand, becomes either acidic at pH 5 or alkaline at pH 8.
Water Balance
Aldosterone
Plasma Volume
ADH

47. Aldosterone
A steroid hormone (mineralocorticoid) synthesized from cholesterol by the enzyme aldosterone synthase.
It is formed in the outer-section (zona glomerulosa) of the adrenal cortex of the adrenal gland.
It helps regulate the body's electrolyte balance by acting on the mineralocorticoid receptor (MR).
It diminishes the excretion of Na+ ions and therefore water, and stimulates the excretion of K+ ions by the kidneys.
Aldosterone is synthesized in reaction to increases of angiotensin II or plasma potassium, which are present in proportion to sodium deficiencies.

48. Control of aldosterone release
The role of baroreceptors
Baroreceptors in the human body detect the pressure of blood flowing though them, and can send messages to the central nervous system to increase or decrease total peripheral resistance and cardiac output.
The role of the juxtaglomerular apparatus
The role of sympathetic nerves
The role of the renin-angiotensin system

49. ADH (VASOPRESSIN)
A human hormone that is mainly released when the body is low on water.
It causes the kidneys to conserve water by concentrating the urine.
If there is not enough water in the body
The osmotic activity of the EC solution is increased → stimulation of the OSMOTIC RECEPTORS in the hypothalamus → stimulation of posterior lobe of the pituitary gland → activation of VASOPRESSIN → increase of the permeability of collecting ductus for the water → reabsorption → HYPERTONIC URINE
If there is too much water in the body
The increase volume stimulates VOLUME RECEPTORS in the heart and big veins and arteries → decrease of the activation of VASOPRESSIN → decrease of the permeability of collecting ductus for the water → water is not reabsorbed → ISO- or HYPOOSMOTIC URINE

50. Renin-angiotensin system 1
A hormone system that helps regulate long-term blood pressure and blood volume in the body.
The system can be activated when there is a loss of blood volume or a drop in blood pressure (such as in a hemorrhage).
If the perfusion of the juxtaglomerular apparatus in the kidneys decreases, then the juxtaglomerular cells release the enzymatic hormone renin.
Activation:
from VOLUME RECEPTORS in afferent arteriole → decrease in perfusion → decrease in tonus of afferent arteriole
from CHEMORECEPTORS in macula densa → decrease of NaCl in macula densa cells

51. Renin-angiotensin system 2

52. Renin-angiotensin system 3
Renin activates the renin-angiotensin system by cleaving angiotensinogen, produced in the liver, to yield angiotensin I, which is further converted into angiotensin II by specialized cells of the lung capillaries.
Angiotensin II then constricts blood vessels, increases the secretion of ADH and aldosterone, and stimulates the hypothalamus to activate the thirst reflex, all these actions leading to increased blood pressure.

53. Renin
Also known as angiotensinogenase, is a circulating enzyme released mainly by juxtaglomerular cells of the kidneys in response to low blood volume or low body NaCl content.
Actions of renin:
Vasoconstriction in efferent arteriole (increase of glomerular filtration)
Peripheral vasoconstriction (increase in blood pressure)
Secretion of aldosterone (reabsorption of Na+ and water)

54. Renin-angiotensin system 4

55. Kinin-kallikrein system
A kinin is any of various structurally related polypeptides, such as bradykinin and kallikrein, that act locally to induce vasodilation and contraction of smooth muscle.
A role in inflammation, blood pressure control, coagulation and pain.
Produced and stored in distal tubule
Function:
vasodilatation
secretion of prostaglandins (PGE2)
decrease of vasoconstriction and antidiuretic effects of angiotenzin II.
increase of vasodilatation and diuretic effect of kinins

56. Prostaglandins
A prostaglandin is any member of a group of lipid compounds that are derived from fatty acids and have important functions in the animal body.
Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring.
Hormone-like substances
Function:
Vasodilatation
Increase of perfusion
Decrease of water reabsorption
Decrease of active Na+ transport in tubules

57. Parathyroid hormone Function:
PTH is secreted by the parathyroid glands
Function:
regulation of calcium and phosphates excretion by urine
increase of Ca2+ reabsorption in distal tubule and collecting ductus
inhibition of phosphates reabsorption in proximal and distal tubules (increase of their excretion)
decrease in natrium and bicarbonates reabsorption = decrease in water reabsorption