Urinary System

1. Urinary System Presented by Yvonne Tsitsiou 21/05/19

2. Lecture 1 – The Urinary System

3. Learning Objectives • Urinary system: summarise the gross anatomy of the urinary system • Ureters: recall the functional anatomy of the ureters and mechanisms preventing reflux of urine • Bladder: recall the structural and functional anatomy, and histological features of the bladder; recall the mechanisms involved in reflex contraction in response to distension • Urinary sphincters: compare the sphincter urethrae and sphincter vesicae muscles and their nerve supplies • Kidney: recall the macroscopic structure of the kidney and be able to identify theses structures in histological sections • Renal vessels: explain the anatomy of blood vessels in the kidney and their functional significance (including filtration, reabsorption and countercurrent mechanism) 

4. Kidney • Retroperitoneal organ • Surrounded by a dense fibrous capsule • Surrounding that is a fascial pouch which is made of adipose tissue  protects against trauma • Right kidney is 11th intercostal space – due to liver • Left Kidney is at 11th rib • Hilum is at L1 for both • Urinary system: summarise the gross anatomy of the urinary system

5. Posterior relations of the kidney • Urinary system: summarise the gross anatomy of the urinary system

6. Anterior relations of kidney • Right: under liver and hepatic flexure of colon • Left: surrounded by stomach, pancreas, spleen, and splenic flexure • Urinary system: summarise the gross anatomy of the urinary system

7. Ureters • Run vertically down posterior abdominal wall • Run along vertical plane of transverse processes of lumbar vertebrae • They cross the pelvic brim anterior to the sacro-iliac joint & bifurcation of the common iliac arteries • The bladder is anterior so the ureters must come forward around the rectum (and uterus) to reach the bladder • Enter bladder at level of ischial spine • Ureters: recall the functional anatomy of the ureters and mechanisms preventing reflux of urine

8. Macroscopic structure of the kidney • Each kidney has superior and inferior pole • Granular cortex and an inner striated medulla because of the regular arrangement of the tubules and vessels • Human kidney is multilobular • Pyramids  papilla  minor calyx  major calyx  renal pelvis  ureter  bladder • Kidney: recall the macroscopic structure of the kidney and be able to identify theses structures in histological sections

9. Mechanisms preventing reflux of urine • The muscles of the bladder run obliquely so they put pressure on the anterior wall of the ureter preventing reflux • A valve at the vesicoureteral (ureter-bladder) junction prevents backflow of urine • Ureters: recall the functional anatomy of the ureters and mechanisms preventing reflux of urine

10. Bladder • Triangular pyramid with the apex anterior and the base posterior • Apex is behind the pubic symphysis • Lined by urothelium (transitional epithelium) • 3 layered epithelium - slow cell turnover • Large luminal cells have highly specialised low-permeability luminal membrane - prevents dissipation of urine-plasma gradients • Bladder is folded so that it can expand • Urethra passes through peroneal membrane • Female urethra passes straight into the perineum • Male crosses the prostate gland Posterior Anterior • Bladder: recall the structural and functional anatomy, and histological features of the bladder; recall the mechanisms involved in reflex contraction in response to distension

11. Bladder contraction • Occurs in response to distension • Bladder: recall the structural and functional anatomy, and histological features of the bladder; recall the mechanisms involved in reflex contraction in response to distension

12. Urinary Sphincters • Sphincter vesicae (internal sphincter – smooth muscle) • At neck of bladder • Bladder wall tension causes reflex opening • Relaxed by PNS • Contracts by SNS • Sphincter urethrae (external sphincter – striated muscle) • In perineum • Tone maintained by pudendal nerve • Opened by voluntary inhibition of nerves • Urinary sphincters: compare the sphincter urethrae and sphincter vesicae muscles and their nerve supplies

13. Lymph drainage • Follows renal vessels to the renal lymph nodes • Ureter lymph vessels drain into deep iliac and common iliac nodes and you can palpate them in the groin

14. Q: What are the differences between male and female urethras?

15. ARQ Assertion: The left kidney is slightly lower than the right Reason: The liver pushes the kidney down • True True – reason is correct explanation • True True – reason is NOT correct explanation • True False • False True • False False

16. SBA What does bladder contraction occur in response to? • Sympathetic stimulation • Parasympathetic stimulation • Distension from bladder filling • Voluntary muscle contraction • Endocrine signalling

17. Lecture 2 – Structural Basis of Kidney Function

18. Learning Objectives • Renal mechanisms: identify the mechanisms by which solutes enter and leave the tubular fluid and define the role that these mechanisms play in excretion of waste, define reabsorption and secretion; explain the meaning of transcellular and paracellular transport • Renal physiological functions: recall the physiological functions of the kidney including role in homeostasis, excretory function and endocrine function • Nephron: recall the constituent parts of a nephron and which compounds are absorbed in each area, explain the microscopic anatomy of the Bowman's capsule and list the regional features of tubular cells aiding urinary concentration, identify different sections and cell types of the nephron in light and electron microscopic images. • Renin-Angiotensin-Aldosterone Axis: recall the site of secretion of aldosterone and explain influences on rate of production, recall the physiological action of aldosterone and effect on sodium handling; list the effects of angiotensin II on renal function; recall stimuli for renin release; explain the effects of hyper- and hypo-aldosteronism

19. The body needs 2 litres of water a day –from food and drink Function of kidney: • Selective reabsorption occurs in the nephron to keep useful products • Tubular secretion of some components • Concentration of urine as necessary Renal physiological functions: recall the physiological functions of the kidney including role in homeostasis, excretory function and endocrine function

20. Integrated functions of kidney Renal physiological functions: recall the physiological functions of the kidney including role in homeostasis, excretory function and endocrine function

21. Production of urine • Filtration: Blood passing through the glomerulus is filtered and then everything lower than 50 000 molecular weight is filtered • Reabsorption: mainly occurs in the PCT includes ions, glucose, aa, small proteins, water etc. • Creation of Hyper-osmotic ECF: main function of the loop of Henle and vasa recta (blood vessels) – via Countercurrent mechanism • Adjustment of ion content of urine: DCT • Concentration of urine: Collecting duct = ADH Renal mechanisms: identify the mechanisms by which solutes enter and leave the tubular fluid and define the role that these mechanisms play in excretion of waste, define reabsorption and secretion; explain the meaning of transcellular and paracellular transport

22. Filtration – 3 layers • In the glomerulus, afferent arterioles are wider than efferent which allows an increase in BP (narrowing generates pressure) allowing ultrafiltration • 3layers form a mesh which filters the blood • Fenestrated endothelium • Modified basement membrane • Podocytes • Filtrate passes through the Bowman’s capsule to the PCT - isotonic at this point • Nephron: recall the constituent parts of a nephron and which compounds are absorbed in each area, explain the microscopic anatomy of the Bowman's capsule and list the regional features of tubular cells aiding urinary concentration, identify different sections and cell types of the nephron in light and electron microscopic images.

23. Reabsorption PCT • 70% of fluid reabsorbed • Na+ uptake by basolateral Na+ pump  water follows via aquaporins • Glucose reabsorbed by SGLT channel (Na+/glucose co-transporter) • Amino acids by Na+/aa co transporter • Proteins taken up by endocytosis • Lots of mitochondria due to high energy requirement • Nephron: recall the constituent parts of a nephron and which compounds are absorbed in each area, explain the microscopic anatomy of the Bowman's capsule and list the regional features of tubular cells aiding urinary concentration, identify different sections and cell types of the nephron in light and electron microscopic images.

24. Hyper-osmotic Interstitium Loop of Henle • Descending limb is thin and permeable to water • Ascending limb is thick and impermeable to water • Na+/2Cl-/K+ triple transporter pumps ions out of tubular fluid • Lots of mitochondria • Blood vessels (vasa recta) are also arranged in a loop • Creates hyper-osmotic gradient • Nephron: recall the constituent parts of a nephron and which compounds are absorbed in each area, explain the microscopic anatomy of the Bowman's capsule and list the regional features of tubular cells aiding urinary concentration, identify different sections and cell types of the nephron in light and electron microscopic images.

25. Adjustment of ion content Mainly DCT • Under the control of aldosterone which alters sodium potassium balance • Macula densa detects changes in tubular fluid sodium - this is how BP is modified • Nephron: recall the constituent parts of a nephron and which compounds are absorbed in each area, explain the microscopic anatomy of the Bowman's capsule and list the regional features of tubular cells aiding urinary concentration, identify different sections and cell types of the nephron in light and electron microscopic images.

26. Concentration of urine • Collecting duct • Water reabsorption under ADH control • Rate of water movement depends on aquaporin-2 in apical membrane • Basolateral membrane has aquaporin-3, not under control • See endoppt for aquaporin detail • Nephron: recall the constituent parts of a nephron and which compounds are absorbed in each area, explain the microscopic anatomy of the Bowman's capsule and list the regional features of tubular cells aiding urinary concentration, identify different sections and cell types of the nephron in light and electron microscopic images.

27. Juxtaglomerular apparatus • Endocrine cells • macula densa of DCT – senses conc of NaCl in tubular fluid • juxtaglomerular cells of afferent arteriole - senses stretch in arteriole wall • Secretes renin to control blood pressure via angiotensin • LOW BP  sensed by JGA  makes renin  converts angiotensinogen to AT1  ACE converts to AT2  AT2 increases aldosterone production, increases sodium and water reabsorption and causes vasoconstriction • Renin-Angiotensin-Aldosterone Axis: recall the site of secretion of aldosterone and explain influences on rate of production, recall the physiological action of aldosterone and effect on sodium handling; list the effects of angiotensin II on renal function; recall stimuli for renin release; explain the effects of hyper- and hypo-aldosteronism

28. Aldosterone is secreted from the zona glomerulosa of the adrenal cortex • Stimuli for renin release: • Low Na+ (low Na=low GFR=low BP) • Low BP – juxtaglomerular cells act like baroreceptors • SNS – beta 1 receptors on juxtaglomerular cells • (high K+) • Renin-Angiotensin-Aldosterone Axis: recall the site of secretion of aldosterone and explain influences on rate of production, recall the physiological action of aldosterone and effect on sodium handling; list the effects of angiotensin II on renal function; recall stimuli for renin release; explain the effects of hyper- and hypo-aldosteronism

29. ARQ Assertion: The afferent arteriole is wider than the efferent arteriole in the glomerulus Reason: This allows greater blood flow to supply very active cells of the glomerulus • True True – reason is correct explanation • True True – reason is NOT correct explanation • True False • False True • False False

30. SBA Where is the majority of the water reabsorbed? • PCT • Descending limb of loop of Henle • Ascending limb of loop of Henle • DCT • Collecting duct

31. Lecture 3 – Renal Blood Flow and Glomerular Filtration

32. Learning Objectives • Renal blood flow: recall what proportion of cardiac output normally perfuses the kidney, explain the effect of changes in renal blood flow on glomerular filtration rate (GFR) and be able to calculate renal plasma flow rate given appropriate values. • Glomerular filtration: define the term freely filtered, recall the factors affecting filtration of substances in the glomerulus, compare the composition of the glomerular filtrate and the plasma, define glomerular filtration rate and filtration fraction and recall normal values. • Filtration pressure: explain net filtration pressure (hydrostatic and oncotic pressures), explain how net filtration pressure may be affected by changes to either of these components (including arterial blood pressure, plasma protein concentration and ureteral obstruction). • Renal clearance: define renal clearance, explain the use of renal clearance in assessing renal function, and be able to perform the appropriate calculation given appropriate values.

33. Glomerular Filtration • Definition: formation of an ultrafiltrate of plasma in the glomerulus • Kidney failure is an abrupt fall in GF • Passive process - driven by by hydrostatic pressure • Small solutes are freely filtered - same concentration in the filtrate as the plasma

34. Basic Renal Process Primary urine Renal input = renal artery Amount excreted Amount secreted Amount absorbed Amount filtered - = + Renal output = renal vein and ureter Not all substances undergo all processes

35. Glomerular Filtration Pressure • Driving force = glomerular capillaries pressure (Pgc) • - hydrostatic pressure due to BP • Opposing pressures: • hydrostatic pressure of tubule (Pt) • osmotic pressure of plasma proteins in glomerular capillaries (πgc) • Together= net ultrafiltration pressure (Puf) • Puf = Pgc- Pt - πgc • Net filtration = 10-20mmHg • Filtration pressure: explain net filtration pressure (hydrostatic and oncotic pressures), explain how net filtration pressure may be affected by changes to either of these components (including arterial blood pressure, plasma protein concentration and ureteral obstruction).

36. Glomerular Filtration rate GFR = PufxKf • Where Kf is an ultrafiltration coefficient (membrane permeability and area available for filtration). • Any changes in filtration forces or Kf will result in GFR imbalances. • Kidney diseases may reduce number of functioning glomeruli = reduced surface area = fall in Kf so lower GFR • Dilation of glomerular arterioles by drugs/hormones will increase Kf • Glomerular filtration: define the term freely filtered, recall the factors affecting filtration of substances in the glomerulus, compare the composition of the glomerular filtrate and the plasma, define glomerular filtration rate and filtration fraction and recall normal values.

37. Renal Blood Flow • RBF is 1L/min which is 1/5 of cardiac output • Renal plasma flow is 0.6 L/min • Filtration Fraction (FF) = 0.2 because 20% is flitered • Normal GFR is 120 mL/min • Glomerular filtration rate (GFR) = RPF x FF 80% 20% 100% • Renal blood flow: recall what proportion of cardiac output normally perfuses the kidney, explain the effect of changes in renal blood flow on glomerular filtration rate (GFR) and be able to calculate renal plasma flow rate given appropriate values.

38. Autoregulation of GFR • DECREASED GFR • Not filtering enough • Constrict afferent arteriole, dilate efferent arteriole  glomerular capillary pressure decreases • More time for kidneys to filter plasma • INCREASED GFR • Filtering too much (too many ions/ solutes lost in tubular fluid) • Dilate afferent arteriole, constrict efferent arteriole  glomerular capillary pressure increases • Plasma passes through quickly, so less time for filtration Renal sympathetic nervous system: recall the effect of the sympathetic nervous system on the renal vasculature and renin release

39. Mechanisms of Autoregulation • Myogenic mechanism • Vascular smooth muscle constricts when stretched • Keeps GFR constant when BP  • Arterial pressure  afferent arteriole stretched  arteriole contracts  (vessel resistance ) blood flow , GFR constant 2. Tubuloglomerular feedback • Where NaCl in fluid sensed by macula densa in JGA  signal to afferent arteriole  constriction  decreased filtration Renal sympathetic nervous system: recall the effect of the sympathetic nervous system on the renal vasculature and renin release

40. Clearance https://www.youtube.com/watch?v=zurZSXCO-Tw • Clearance is the number of litres of plasma that are completely cleared of the substance per unit time • C = U x V ml/min P If a molecule is freely filtered and not reabsorbed/ secreted in the nephron then the amount filtered = amount excreted GFR is measured by measuring the clearance of a freely filtered molecule e.g. insulin and creatinine Build up of creatinine = fall in GFR = renal disease U = concentration of substance in urine V = rate of urine production P = concentration of substance in plasma • Renal clearance: define renal clearance, explain the use of renal clearance in assessing renal function, and be able to perform the appropriate calculation given appropriate values.

41. Renal diagnostics •  GFR = cardinal feature of renal disease • If GFR , excretory products build up in plasma • important with drugs- could accidently overdose as it isn’t excreted •  plasma conc of creatinine is diagnostic of renal disease • Excretion of many other substances also impaired in renal failure- including some drugs • needs to be taken into account when calculating drug doses Measurement of renal function: recall methods of estimating global renal function and compare advantages and disadvantages of each 

42. ARQ Assertion: When there is a high GFR, the afferent arteriole is constricted and the efferent is dilated Reason: This decreases glomerular capillary pressure allowing less time for filtration • True True – reason is correct explanation • True True – reason is NOT correct explanation • True False • False True • False False

43. SBA What proportion of the cardiac output normally perfuses the kidney? • 50% • 30% • 20% • 10% • 5%

44. Lecture 4 – Basic Tubular Function

45. Learning Objectives • Renal Mechanisms: identify the mechanisms by which solutes enter and leave the tubular fluid and define the role that these mechanisms play in excretion of waster, define reabsorption and secretion; explain the meaning of transcellular and paracellular transport. • Proximal tubule: recall the microscopic structure of the early proximal tubule (including tubular fluid, luminal membrane, basolateral membrane, peritubular capillary, tight junction, Na+/K+ pump); recall examples of ion transport (including ion-selective channel, co-transport of two solutes, counter-transport of two solutes) and explain the role of mutations to identifies transporters in causing renal dysfunction, recall the proportion of solute reabsorbed in this region and contrast this with the distal nephron. • Osmolarity: define osmolarity, define the minimum and maximum urine osmolarity in humans, explain how the kidney produces dilute and concentrated urine and explain why this is dependent on the osmolarity of the medullary and papillary interstitium, and permeability of the collecting ducts; explain how changes in plasma osmolarity and volume affect thirst, explain how and why osmolarity varies along the nephron • Vasopressin: explain the mechanisms controlling vasopressin release (including hypothalamic osmoreceptors) and recall the physiological action of vasopressin on the renal tubule

46. Osmolarity • The kidney is a central regulator of homeostasis OSMOLARITY: a measure of the osmotic pressure exerted by a solution across a perfect semi-permeable membrane. dependent on the number of particles in the solution all the concentrations of the different solutes added together normal plasma osmolarity is tightly controlled 285-295 mosm/kg Osmolarity: define osmolarity, define the minimum and maximum urine osmolarity in humans

47. Renal Tubular Wall • Single layer of cells • Between the cells are tight junctions that vary in their tightness depending on where you are in the system • Secretion and reabsorption both occur either by transcellular or paracellular transport • Through cells- transcellular • Between cells- paracellular • Renal Mechanisms: identify the mechanisms by which solutes enter and leave the tubular fluid and define the role that these mechanisms play in excretion of waster, define reabsorption and secretion; explain the meaning of transcellular and paracellular transport.

48. Passive movement • Linear • non saturable- hydrophobic molecules rate Solute concentration Protein independent transport (lipophilic molecules) rate • Saturable • Non linear Solute concentration Protein dependent transport (hydrophilic molecules) • Renal Mechanisms: identify the mechanisms by which solutes enter and leave the tubular fluid and define the role that these mechanisms play in excretion of waster, define reabsorption and secretion; explain the meaning of transcellular and paracellular transport.

49. ATP ADP + Pi Active movement – Cellular Energy dependent ATP rate ADP + Pi Solute concentration Directly coupled to ATP hydrolysis Na+ rate Na+ K+ Glucose Solute concentration Indirectly coupled to ATP hydrolysis

50. Transport maxima • It is the point at which a rise in solute concentration does not yield a rise in rate. • Limit to what can enter/exit cells • Applies to whole system, not just individual cells • Can vary depending on circumstances, stimulated maximum higher than basal max • Normally exceeds requirement • Amount of glucose filtered plasma glucose concentration • Up to certain plasma glucose concentration, all glucose is reabsorbed • Above certain plasma glucose concentration, can’t absorb any more so it is excreted  diabetes mellitus