1. Chapter 26: The Urinary System
3 Lectures:
Gross Anatomy of Kidneys
How filtrate is formed and how the rate of filtration (GFR) is controlled
Tubular reabsorption and secretion

2. Kidneys (2), ureters (2), urinary bladder (1) & urethra (1)
Kidneys filter blood plasma and returns water and solutes back to blood
What remains is urine
Urine flows from each kidney, down its ureter to the bladder and to the outside via the urethra

3. Overview of Kidney Functions
Regulation of blood ionic composition
Na+, K+, Ca+2, Cl- and phosphate ions
Regulation of blood pH
H+ and HCO3
Regulation of blood volume
conserving or eliminating water
Regulation of blood pressure
Excretion of wastes
Production of hormones (erythropoietin & calcitriol)
Help maintain Homeostasis

4. External Anatomy of the Kidneys
Paired kidneys - kidney-bean-shaped
Located just above the waist between the peritoneum & posterior wall of abdomen
retroperitoneal along with adrenal glands & ureters
Protected by 11th & 12th ribs
Right kidney lower because of liver
Renal hilus – where ureters and blood vessels enter/exit

5. External Layers of the Kidney
Renal Capsule – Deepest
smooth transparent sheet of dense irregular connective tissue–helps maintain the shape of the kidney
Adipose Capsule – Intermediate
protects the kidney from trauma
Renal Fascia – Superficial
anchors kidney to the surrounding structures and to the abdominal wall

6. POSTERIOR

7. Internal Anatomy of the Kidneys
Two Distinct Regions:
Renal Cortex:
Superficial light red region
Renal Medulla
Deep, dark reddish-brown region
consists of 8-18 cone-shaped renal pyramids separated by renal columns
renal papilla point toward the Renal hilum
Together the Renal Cortex and the Renal Medulla constitute the parenchyma – functional portion of kidney

9. Number of Nephrons Remains constant from birth – one million
any increase in size of kidney results in an increase in size of individual nephrons
If injured, no replacement occurs
Dysfunction is not evident until function declines by 25% of normal (other nephrons handle the extra work)
Removal of one kidney causes enlargement of the remaining until it can filter at 80% of normal rate of 2 kidneys

10. The Nephron – functional unit of kidney
Renal Corpuscle: filtration
Gomerulus
Glomerular capsule (Bowman’s capsule)
Renal Tubules: reabsorption & secretion
Proximal convoluted tubule (PCT)
Nephron loop (loop of Henle)
Distal convoluted tubule (DCT)
DCTs of several nephrons empty into a single Collecting Duct

11. Juxtamedullary Nephrons – 15%
Two Types of Nephrons
Cortical Nephrons – 85%
Juxtamedullary Nephrons – 15%

12. Glomerular (Bowman’s) Capsule
Bowman’s capsule surrounds glomerulus forming capsular space
Two layers of capsule:
Visceral layer – Podocytes – “foot cells” modified simple squamous
Parietal layer – Simple squamous epithelium
Think of it as a fist punched into an inflated bag

13. Histology of Renal Tubule & Collecting Duct
Proximal convoluted tubule (PCT)
simple cuboidal with brush border of microvilli - increase surface area for absorption
Descending limb of loop of Henle
simple squamous
Ascending limb of loop of Henle
simple cuboidal
forms juxtaglomerular apparatus (JGA) where makes contact with afferent arteriole
Distal convoluted & collecting ducts
simple cuboidal composed of principal & intercalated cells which have microvilli

14. Macula densa is thickened part of ascending limb of Loop of Henle
Juxtaglomerular (JG) cells are modified muscle cells in afferent arteriole
Together form Juxtaglomerular apparatus (JGA) – helps regulate blood pressure
Mesangial cells – specialized smooth muscle
Relaxed – increases surface area – increases filtration
Contracted – decreases surface area – decreases filtration

15. Blood Supply of Kidney Abundantly supplied with blood vessels
receive 25% of resting cardiac output via renal arteries
Blood enters kidney via Renal Artery
Radiate outward into renal cortex - branch off into Afferent arterioles (one per nephron)
Enters nephron and becomes a ball-shaped capillary network called Glomerulus (filtration)
Leaves nephron as Efferent arteriole
Efferent arteriole divides to either Peritubular capillaries (Cortical nephron) or Vasa recta (Juxtamedullary nephron)
Blood leaves kidney via Renal Vein

17. From Renal Artery
Renal Vein

18. Summary of Renal Anatomy
2 kidneys (retroperitoneal), 2 ureters, 1 bladder, 1 urethra
3 layers – Renal capsule (deepest), Adipose capsule (intermediate), Renal Fascia (superficial)
Parenchyma = Cortex + Medulla
Functional portion of kidney
Nephrons = functional units (cortical + juxtamedullary)
Nephron:
Renal (Bowman’s) capsule – parietal layer + visceral layer
PCT – Simple cuboidal with microvilli
Loop of Henle – Thin descending + Thick ascending
DCT
Collecting Duct – Principal + Intercalated cells
Drainage system collects fluid from nephrons
Minor calyx – Major calyx – Renal pelvis – Ureter – Bladder – Urethra
Blood Supply:
Renal Artery
Afferent Arteriole
Glomerulus
Efferent Arteriole – Peritubular capillaries + Vasa recta
Renal Vein

19. Nephrons and collecting ducts perform 3 basic processes:
1. Glomerular filtration – water and most solutes
2. Tubular reabsorption – 99% of water and many useful solutes back into blood
3. Tubular secretion – waste, drugs, excess ions from blood to tubules

20. Glomerular Filtration
Blood pressure produces glomerular filtrate
180 litres/day filtrate produced
99% reabsorbed to blood
1-2 L/day urine
Substances filtered out must cross 3 filtration barriers of the endothelial-capsular membrane:
Glomerular endothelial cell fenestrations
Basal lamina
Pedicels of podocytes – filtration slits

21. Filtration Membrane
#1 Endothelial fenestrations - Stops all cells and platelets
#2 Basal Lamina - Stops large plasma proteins
#3 Podocytes - Pedicels (filtration slits) - Stops medium-sized proteins

23. Endothelial-Capsular Membrane

24. 3 Reasons why the volume of fluid filtered by the renal corpuscle is much larger than in other blood capillaries:
Large surface area regulated by Mesangial cells. When cells are relaxed, surface area is maximal and filtration rates are high.
Filtration membrane is thin and porous – 50x leakier than other blood capillaries
Glomerular capillary blood pressure is high – efferent arteriole diameter is smaller than afferent arteriole.

25. Glomerular Filtration depends on 3 main pressures:
One pressure promotes filtration
Two pressures oppose filtration
Glomerular blood hydrostatic pressure (GBHP) – 55 mmHg
Promotes filtration by forcing water and solutes through filtration membrane
2. Capsular hydrostatic pressure
(CHP) – 15 mmHg
Opposes filtration by exerting back pressure against filtration membrane
3. Blood colloid osmotic pressure
(BCOP) – 30 mmHg
Opposes filtration by the presence of proteins in blood plasma which slows down osmosis

26. Net Filtration Pressure (NFP)
GBHP = 55 mmHg - Promotes
CHP = 15 mmHg - Opposes
BCOP = 30 mmHg - Opposes
Net Filtration Pressure (NFP)
= GBHP – CHP – BCOP
= 55 –
= 10 mmHg
Therefore, a pressure of only 10 mmHg causes a normal amount of blood plasma to filter from the glomerulus into the capsular (Bowman’s) space.
Changes to either of these three pressures will affect the Glomerular Filtration Rate (GFR)

27. Glomerular Filtration Rate (GFR)
Amount of filtrate formed in all renal corpuscles of both kidneys - average adult male rate is 125 mL/min
Homeostasis requires GFR to be constant
too high & useful substances are lost due to the speed of fluid passing through nephron
too low and sufficient waste products may not be removed from the body
Three mechanisms control GFR by either (a) adjusting blood flow in/out of glomerulus (JGA) or (b) altering capillary surface area for filtrations (mesangial cells). (Table 26.2 pg. 996)
Renal autoregulation
Neural regulation
Hormonal regulation

28. 1. Renal Autoregulation of GFR
Kidneys themselves help maintain a constant GFR despite normal, everyday changes in blood pressure (BP)
Myogenic mechanism
systemic increases in BP also increase GFR
Increases to BP stretch the afferent arteriole
smooth muscle fibers contract, reducing the diameter of the arteriole – decreasing blood flow and GFR
Tubuloglomerular feedback
elevated systemic BP raises the GFR - fluid flows too rapidly through the renal tubules & Na+, Cl- and water are not reabsorbed quickly enough
macula densa detects that difference & inhibit release of NO (vasodilator) from the Juxtaglomerular cells
afferent arterioles constrict & reduce GFR

29. Tubuloglomerular feedback:
Myogenic mechanism:
Increase in BP stretches walls of Afferent arteriole
Smooth muscles in vessel walls contract
Blood flow decreases which lowers GFR
Tubuloglomerular feedback:
Macula densa detect changes to filtrate
Inhibit release of NO (potent vasodilator) by Juxtaglomerular cells
Afferent arteriole contracts

30. 3. Hormonal Regulation of GFR
Two hormones contribute to regulation of GFR:
Atrial natriuretic peptide (ANP) – increases
Angiotensin II – decreases
Atrial Natriuretic Peptide (ANP):
stretching of the atria that occurs with an increase in blood volume causes cells of atria to release ANP
relaxes glomerular Mesangial cells, therefore increasing capillary surface area and increasing GFR
Angiotensin II:
Release stimulated by decrease in blood volume/pressure
Enzyme Renin secreted by juxtaglomerular cells
potent vasoconstrictor that narrows both afferent & efferent arterioles decreasing GFR

31. Summary of Filtration Occurs in Renal Corpuscle
Substances filtered across 3 filtration barriers (endothelial-capsular membrane):
Glomerular endothelial cell – fenestrations make it very porous (leaky)
Basal lamina
Pedicels of podocytes – filtration slits
Filtration is dependent on 3 pressures:
Glomerular blood hydrostatic pressure (GBHP) - promotes
Capsular hydrostatic pressure (CHP) - opposes
Blood colloid osmotic pressure (BCOP) – opposes
Net Filtration Pressure = GBHP – CHP – BCOP
Determines Glomerular Filtration Rate (GFR)
Must remain constant
GFR regulated by 3 mechanisms
Renal Autoregulation :
Myogenic mechanism
Tubulogomerular feedback
Neural Regulation – ANS – “Fight or Flight”
Hormonal Regulation
Angiotensin II – Decreases GFR
Atrial natriuretic peptide (ANP) – Increases GFR

32. 1. Glomerular filtration – water and most solutes
2. Tubular reabsorption – 99% of water and many useful solutes back into blood
3. Tubular secretion – waste, drugs, excess ions from blood to tubules

33. Tubular reabsorption Paracellular reabsorption
Epithelial cells all along the renal tubules and collecting duct carry out reabsorption
Proximal convoluted tubules (PCT) make largest contribution
More distal tubule cells fine-tune reabsorption to maintain homeostasis
Paracellular reabsorption
50% of reabsorbed material moves between cells by diffusion in some parts of tubule
Transcellular reabsorption
material moves through both the apical and basolateral membranes of the tubule cell

34. Reabsorption in the PCT
Largest amount of solute and water reabsorption occurs in PCT
65% of filtered water, Na+ and K+
100% of glucose and amino acids
80-90% of HCO3
Most solute reabsorption in PCT involves Na+
Water is only reabsorbed by osmosis:
obligatory water reabsorption occurs when water is “obliged” to follow the solutes being reabsorbed
facultative water reabsorption occurs in collecting duct under the control of antidiuretic hormone (ADH)

35. Reabsorption of Glucose in PCT
Intracellular sodium levels are kept low due to Na+/K+ ATPase pump on basolateral membrane
Low intracellular Na+ creates concentration gradient
high in filtrate – low in cell
Na+ symporters on apical membrane use energy from gradient to bring in glucose
Secondary active transport
2 Na+ and 1 glucose attach to symporter and enter cell together
Glucose then diffuses out of cell and into peritubular capillaries

36. Reabsorption of Bicarbonate & H+ ion secretion in PCT
CO2 + H2O H2CO HCO3- + H+

37. Reabsorption within Loop of Henle
Osmolarity of interstitial fluid progressively increases deeper into the medulla
Descending loop is highly permeable to water. Water moves by osmosis out of the tubule (15% of total reabsorption) increasing filtrate concentration
Thick ascending loop has many Na+, K+ and Cl- transporters. Ions pass out of filtrate and into intersitital fluid (20-30% total reabsorption)
These cells are also impermeable to water, so water does not follow osmotically.
Therefore decreasing concentration/osmolarity of filtrate
This osmotic gradient is how the kidneys are able to produce concentrated or dilute urine.

38. Reabsorption in Early DCT Reabsorption in late DCT & Collecting Ducts
Absorb 10-15% of water and 5% of Na+ and Cl-
Also where parathyroid hormone (PTH) stimulates reabsorption of Ca2+ depending on body’s needs.
Reabsorption in late DCT & Collecting Ducts
By end of DCT, 95% of solutes & water have been reabsorbed and returned to the bloodstream
Cells in the collecting duct make the final fine tuning adjustments:
principal cells reabsorb Na+ and secrete K+; facultative reabsorption of H2O (ADH)
intercalated cells reabsorb K+ & bicarbonate ions (HCO3) and secrete H+ (regulate pH)
Hormonally controlled by Angiotensin II, Aldosterone, Atrial natriuretic peptide (ANP) , Antidiuretic hormone (ADH) and Parathyroid hormone

39. Angiotensin II and Aldosterone
When blood volume/pressure drop – JG cells secrete renin
Renin helps convert angiotensin I – angiotensin II (active)
decreases GFR by vasoconstricting afferent arteriole
enhances absorption of Na+, Cl- and water in PCT
promotes aldosterone production (adrenal gland) which causes principal cells to reabsorb more Na +,Cl-, and water
increases blood volume/pressure by increasing water reabsorption
Atrial Natriuretic Peptide (ANP)
Stimulated by large increase in blood volume
inhibits reabsorption of Na + and water in PCT & suppresses secretion of aldosterone & ADH
increase excretion of Na + into tubules (obligated water) which increases urine output and decreases blood volume

40. Antidiuretic Hormone (ADH)
Released by posterior pituitary
Stimulated by an increased plasma osmolarity or a decrease in blood volume (hemorrhage)
Stimulates the insertion of aquaporin-2 channels into the apical membrane of principal cells of late DCT and collecting duct– greatly increases permeability of cells and reabsorption of water from filtrate (concentrated urine)
In absence of ADH, principal cells of DCT and collecting ducts are impermeable to water – no water is reabsorbed therefore increasing urine output (dilute urine)
Diabetes insipidus – lack of ADH or insensitive to it
excrete 20L urine/day

41. Breaking The Seal Alcohol inhibits release of ADH
Without ADH, DCT and collecting ducts are impermeable to water
Kidneys can’t reabsorb needed water – instead produce copious amounts of dilute urine
Effects of alcohol linger long after you stop drinking – leaving you feeling dehydrated

42. Summary – Absorption & Secretion