Urinary System Concepts

Question 1

Name and briefly describe 4 major functions of the urinary system

Answer 1

Regulation of blood ionic composition, blood pH, and blood osmolarity

Regulation of blood volume and blood pressure

Endocrine production of renin, calcitriol, and erythropoietin

Excretion of waste

Question 2

Describe how the urinary system is probably the major player in controlling critical blood composition parameters.

Answer 2

The urinary system has a huge role in setting the blood parameters by reabsorbing (or not) various ions. pH is set simply by H+ movement. The overall ionic strength of a solution is basically just the osmolarity (~290mOsm in “normal” blood)

Question 3

Review how the RAAS regulates blood volume & blood pressure. Tie in the work of ADH, too, here.

Answer 3

• The kidney determines the amount of water in the circulatory system by reabsorbing lots (or not) of water from the loop of Henle and the distal collecting tubule.
• An increase of water in the blood means an increase in blood volume and blood pressure. Decrease water in the blood means decreased blood volume and blood pressure.
• ADH increases blood volume and blood pressure as it pulls out Na back into the blood, and wherever Na goes, water follows.

Question 4

Connect urea formation and appearance in the urine to deamination of amino acids entering the Krebs Cycle.

Answer 4

Deaminating amino acids (cutting up) to put them into the Krebs cycle creates urea (toxin) which you excrete in urine

Question 5

Give a brief overview of the macro anatomy of the kidney, focusing on location, shape, blood supply, the 3-part external covering (and how it relates to the parietal peritoneum), the cortical-medullar split of renal tissue, the lobes, columns, pyramids, papillae and nephrons of the kidney

Answer 5

• “Kidney” shaped
• Heavily vascularized - The entire blood supply of the body is fed through kidneys every 5-6 minutes
• Retroperitoneal, about the level of the floating ribs, and the right sits slightly lower than the left
• 3 part external covering deep to superficial: fibrous capsule (renal capsule), perirenal fat capsule (adipose capsule), renal fascia. These are deep to the parietal peritoneum.
• The functional unit of the kidney is the nephron (there are about 2 million). They start in the cortex and end roughly at the hilum.
• Divided into 8-12 lobes, which are separated by renal columns which are extensions of the cortex all the way down almost to the hilum
• Each lobe has a superficial cortex, deeper medulla, and half of each renal column flanking the lobe. A pyramid, the triangular shape, is in each lobe.
• The papillae of the kidney is the deepest part of the pyramid and is at the hilum

Question 6

Summarize, very briefly sympathetic and parasympathetic control over vasoconstriction/vasodilation to control blood supply to the kidney and ultimately GFR.

Answer 6

The sympathetic response will be vasoconstriction to reduce renal activity (filtration/urine volume) during fight or flight

The parasympathetic response would be vasodilation to stimulate renal activity during rest and recover

Question 7

Trace the afferent vascularization from the renal artery to the glomerular capillaries of a “generic nephron.” From there, trace the efferent vascularization from the glomerulus, incorporating vasa recta for juxtamedullary nephrons.

Answer 7

Renal artery to glomerular capillaries:
Renal artery
Segmental A.
Interlobar A.
Arcuate A.
Cortical radiate A.
Afferent glomerular A.
Glomerular C.
Efferent glomerular A.

Efferent:
Peritubular C.
Peritubular V.
Cortical radiate V.
Arcuate V.
Interlobar V.
Renal V.

Question 8

Name the 2 parts to a nephron and the key structures of each part, focusing on the role and cortical or medullar location of each structure.

Answer 8

Renal corpuscle
- Glomerulus
- Glomerular capsule

Renal tubule (more secretion or reabsorption)

Question 9

From the distal end of the nephron, continue to trace the path of urine to the ureter

Answer 9

• From the DCT, urine continues to flow into collecting ducts (leaving the cortex and entering the medulla), then into papillary ducts (deep in the medulla), then into a minor calyx
• From there, urine flows into a major calyx, then into the renal pelvis, and out the kidney via the ureter

Question 10

Contrast the two types of nephrons, focusing on frequency of occurrence, depth of the glomerulus within the cortex, length of the loop of Henle, presence of vasa recta, and ability to make concentrated urine

Answer 10

Cortical Nephrons:
- 80-85%
- Sit in the most superficial part of the cortex, and short loops of Henle dip only briefly into the medulla
- Peritubular capillaries stemming from the efferent arterioles

Juxtamedullary Nephrons:
-15-20%
- Long loops, sit much deeper in the cortex, and their long loops of Henle dip down most of the span of the medulla
- Peritubular capillaries stemming from the efferent arterioles, AND vasa recta capillaries, also stemming from efferent arterioles
- Have 2 parts to the ascending limb - thin and thick
- The extra length of the loop of Henle gives it more capability to secrete/absorb more than cortical nephrons - so it can produce more dilute or concentrated urine

Question 11

Describe the architecture of the nephron that allows the DCT to pass right next to the glomerulus, the reason for this, and the coordinating roles of macula densa and JG cells to kick off the RAAS

Answer 11

• As the ascending limb of the loop of Henle moves back into the cortex, it passes right next to the glomerular capsule and the afferent/efferent arterioles
• The columnar epithelial cells lining the ascending limb condense to become the macula densa
• The macula densa pushes up against some modified smooth muscle cells which are the JG (juxtaglomerular) cells that are squeezed between the macula densa and the endothelial cells lining the afferent (and sometimes) efferent arterioles
• The JG cells sense low blood volume (low BP) and pump renin into the blood to trigger the start of the RAAS

Question 12

Describe glomerular filtration in detail, focusing on the 3 components of NFP, the 3 layers of the filtration membrane, and a general description of what gets filtered (or blocked) at each layer.

Answer 12

The glomerular filtrate is what “gets through” and eventually becomes urine

Net Filtration Pressure: NFP = GBHP - CHP - BCOP
- Glomerular blood hydrostatic pressure (GBHP) is the blood pressure entering glomeruli (high)
- Capsular hydrostatic pressure (CHP) is the pressure of the fluid already in the capsule, opposing filtration (“back pressure”)
- Blood colloid osmotic pressure (BCOP or BOP) is the omosotic pull by mid-large proteins still in the blood - to pull plasma back into the capillaries

3 layers of filtration membrane:
- Fenestration (pore) of glomerular endothelial cells: prevents filtration of blood cells but allows all components of blood plasma to pass through
- Basement membrane of glomerulus: prevents filtrations of larger proteins
- Slit membrane between pedicels: prevents filtration of medium-sized proteins

Question 13

Contrast a true Basal lamina to a Basement membrane, noting how the basement membrane of the kidney is actually constructed

Answer 13

• A true basement membrane will have the basal lamina layers sitting atop a lamina reticularis, which is synthesized by underlying C.T. and has sticky fibronectin to connect C.T. to the basal lamina
• In the kidney, there is no underlying C.T., as it’s two epithelial fused together (capillary endothelial cells and the podocytes of the glomerular capsule (modified simple squamous epithelial cells))
• So what we call the glomerular “basement membrane” is just two basal lamina fused together

Question 14

Describe the structure and function of the glomerular capsule, focusing on the parietal and visceral layer of epithelial cells.

Answer 14

• The glomerular capsule that catches the urine (bowman’s capsule) is lined with epithelial cells continuous with the tubular epithelium
• Filters blood
• The outer part of the capsule is lined by a parietal layer (simple squamous), while the inner portion is the visceral layer (simple squamous modified podocytes) that sits back to back with capillary endothelial cells

Question 15

Contrast briefly the dangers of excess and inadequate GFR.

Answer 15

Excess glomerular filtration rate (GFR) means you’ll have all kinds of stuff in the urine that shouldn’t be

Inadequate GFR means toxins that need to be in the urine may not be there

Question 16

Contrast briefly the two types of autoregulation mechanisms

Answer 16

Myogenic mechanism
If Renal BP climbs (exercise), it will stretch the walls of afferent arterioles, which will “automatically” trigger them to contract, which constricts the lumen and decreases the volume of blood flow

Tubuloglomeruluar feedback
- If systemic BP stays high and GFR climbs despite the myogenic mechanism, fluid will move faster through the proximal tubules, leaving less time to absorb ions. Macula densa cells register increased ion levels in the blood, and via paracrine paths, they’ll inhibit the release of NO from the JGs
- No natural vasodilators, so without NO, afferent arterioles vasoconstrict to limit blood flow into glomeruli

Question 17

Describe briefly neuronal control of GFR

Answer 17

Same story of afferent arteriole vasocontraction, just triggered by NE released by sympathetic fibers of the ANS

With heavy exercise, stress, panic, or any other “fight or flight” reaction, it kicks in to keep GFR in check to offset systemic BP spikes

Question 18

Contrast the 2 hormonal mechanisms of GFR, focusing specifically, with ANP, on the role of the mesangial cells in controlling GFR

Answer 18

Angiotensin II
- Same story of afferent arteriole vasoconstriction, just triggered here by Angiotensin II which is a powerful vasoconstrictor to decrease GFR

ANP
- Only one to increase GFR
- Relaxes mesangial cells, which are contractile cells wedged between afferent and effect arterioles
- Contraction of these cells squeezes glomerular capillaries together and decreases available filtration surface area
- Relaxation increases GFR by “blooming” glomerular capillaries

Question 19

Contrast, very generally, reabsorption & secretion at the renal tubules

Answer 19

Reabsorption is transport from the tubules (filtrate) back into renal capillaries (stuff you had to filter, but now you want back)

Secretion is direct transport of unwanted substances from capillaries into tubules (bypassing glomerular filtration)

Question 20

Be able to name a whole handful of things that are almost always reabsorbed in excess of 95% by the renal tubules.

Answer 20

Water
Proteins
Sodium ions
Chloride ions
Bicarbonate ions
Glucose

Question 21

Name the 3 primary ions that are secreted, along with a couple of metabolites and other
substances that tend to be secreted.

Answer 21

H+, K+, ammonium, creatinine, drugs

Question 22

Identify the primary region of reabsorption and secretion.

Answer 22

Proximal convoluted tubules

Question 23

Describe how the tiniest proteins (that got filtered) are reabsorbed

Answer 23

Small proteins that got through the filter are exclusively reabsorbed, via pinocytosis (or bulk-phase endocytosis, or “cell-drinking”)

Question 24

Describe our “neighborhood birds-eye view”, relating the parts of the neighborhood to the parts of the renal tubule & surrounding structures, focusing on tight junctions, and paracellular vs. transcellular routes

Answer 24

If houses were cells to get from the street to the backyard you could:
Go through the house (transcellular)
Go between the houses (paracellular)

• Tubule cells are epithelial cells (simple squamous, simple cuboidal to low columnar…)
• Epithelial cells are connected by tight junctions
• Tight junctions are little pieces of fencing between houses, making it harder for things to pass between houses
• Some parts of the tubule epithelial membrane have “leaky” tight junctions, so paracellular route may occur

Question 25

Contrast primary and secondary active transport, focusing on the primary mechanism, and describing 3 key secondary active transport mechanisms – an antiport and symport in the PCT and a one key symport in the loop of Henle.

Answer 25

Primary active transport - 3 Na+ are kicked out of the epithelial cells of the renal tubule and into the basolateral interstitial fluid, while 2 K+ are brought into the cell. Both accomplished by the Na+/K+ ATPase pump Secondary active transport - Glucose is reabsorbed from the proximal convoluted tubule back into the blood via symport with 2 Na+ ions - H+ ions are secreted from epithelial cells lining the PCT into the lumen of the PCT via H+/Na+ antiporters - In the ascending limb of the Loop of Henle, huge quantities of Na+ and Cl- are reabsorbed from filtrate by symport of one Na+, one K+, and 2 Cl-

Question 26

Contrast antiport and symport

Answer 26

Antiport Movement of two molecules in the opposite direction through a protein channel Symport Proteins that move two molecules in the same direction

Question 27

Contrast obligatory and facultative water reabsorption, giving the primary location of each.

Answer 27

Obligatory faculative water reabsorption - Wherever Na goes, water follows by osmosis Facultative water reabsorption - the collecting ducts are affected by the ADH, making them permeable to water, triggering water reabsorption into the bloodstream

Question 28

Give a very brief overview of reabsorption and secretion in the PCT, the loop of Henle, the DCT, and the collecting ducts, focusing on the default mechanisms of dilute urine.

Answer 28

PCT: Secondary active antiport to secrete H+ as Na+ is reabsorbed into tubular epithelial cells Loop of Henle: Na and CL are heavily reabsorbed via Na+-K+-2Cl- symporters Parts of the loop that are very impermeable to water If dilute urine is required, this is where tubular filtrate loses tons of ions (but not so much water) DCT: Na-Cl symporters just about finish those 2 off Ca reabsorption is key because parathyroid hormone can act here to strongly modify Ca reabsorption Collecting Ducts: Principal cells finish off the very last bits of Na+ and secrete K+ Interacalatated vells reabsorb last bits of K and HCO3 and secrete H+ if needed

Question 29

Describe the specific locations and mechanisms of action of Angiotensin II, Aldosterone & ADH in conserving water & producing concentrated urine. Contrast the location and mechanism of action of ANP.

Answer 29

Aldosterone and ADH conserve water by producing concentrated urine Angiotensin II: causes the muscular walls of small arteries (arterioles) to constrict (narrow), increasing blood pressure Triggers adrenal glands to release aldosterone and pituitary gland to release ADH Aldosterone: Works on principal cells of the collecting ducts Stimulates “extra” Na+ and Cl- absorption and “extra” K+ secretion ADH: Works on the principal cells of the DCT and collecting ducts These sections of the tubule are usually impermeable to water ADH inserts aquaporin channels into the apical membrane to allow facultative water passage ANP: Undoes just about every action of Angiotensin II, and it inhibits the secretion of aldosterone and ADH Working to combat hypervolemia by decreasing “extra” Na+ and Cl- reabsorption Working against ADH to decrease “extra” facultative water reabsorption

Question 30

Describe the specific location and mechanism of action of PTH in conserving Ca.

Answer 30

Parathyroid hormone works on simple cuboidal cells of the DCT to combat hypocalcemia - Stimulates these cells to reabsorb more Ca from the urine - back into the blood - Another way is to pull Ca out of bones

Question 31

Give a general idea of the components of blood osmolarity

Answer 31

Blood osmolarity is functionally the total concentration of solutes in the fluid - Sodium - Chloride

Question 32

Describe, briefly, the default formation of dilute urine, focusing on the osmolarity of filtrate in the glomerular capsule, in and out of the PCT, out of the loop of Henle and the osmolarity of the final dilute urine. Focus on the water permeability of the epithelial cells of the ascending loop of Henle, late DCT & the principal cells of the collecting ducts

Answer 32

Blood enters the glomerular capillaries at a standard 300, and since formed elements don't contribute, and only the tiniest proteins get through the filtration membrane, the globular filtrate is about 300 as well In the PCT, tons of ions are absorbed, but obligatory water follows ions, in concert, so the overall osmolarity doesn't change through the PCT In the thick ascending limb of the Loop of Henle, tons of ions are still being absorbed, but these epithelial cells are far less permeable to water. So ions are leaving the filtrate, but obligatory water reabsorption slows.. In the DCT and collecting ducts, ions are being reabsorbed by principal cells, but these epithelial cells are impermeable to water (without ADH) so ions are still leaving the filtrate, but obligatory water reabsorption stops…

Question 33

Describe the location and mechanisms of action of ADH to produce concentrated urine, focusing on the osmolarity coming out of the loop of Henle (as compared to that of dilute urine) and the osmolarity of the filtrate through the DCT & collecting ducts.

Answer 33

When youre dehydrated your hypothalamic nuclei sense elevated blood osmolarity and can stimulate your neurohypophysis to secrete ADH ADH will go to the principal cells of the collecting ducts, insert aquaporin (water) channels, and cause facultative water to pour out of the collecting ducts, greatly concentrating the urine Water will only leave the collecting ducts if the surrounding ISF is very highly concentrated with salts The thick ascending limb of the loop of Henle runs “counter” to the collecting ducts and loads the ISF with solutes

Question 34

Briefly describe the role of the countercurrent Exchanger in facilitating water movement out of the collecting ducts to concentrate the urine.

Answer 34

The thick ascending limb of the loop of Henle runs “counter” to the collecting ducts and loads the ISF with solutes. The ISF will be more hypertonic so water is driven into the ISF from the collecting duct, concentrating urine

Question 35

Describe, briefly, lab measurements of GFR and clearance ratios

Answer 35

Glomerular filtration rate: estimates how much blood passes through the glomeruli each minute Clearance ratios: the ratio of the amount of solute excreted in the urine CR < 1 means a substance i net reabsorbed CR > 1 means net secretion

Question 36

Trace flow of urine from the kidney to the external urethral orifice – being sex-specific

Answer 36

From the kidney, run two ureters into the urinary bladder for storage - then 1 urethra from the bladder for micturition Urine moves through the ureters via hydrostatic pressure, peristalsis, and gravity As ureters descend through the abdominopelvic cavity, and approach the bladder, they move medially to enter the bladder through ureteral openings in the posterior wall of the bladder

Question 37

Describe 3 ways urine moves through the ureter.

Answer 37

Hydrostatic pressure, peristalsis, and gravity

Question 38

Discuss how the expansion of the urinary bladder blocks passage in and out of the ureter.

Answer 38

There is no ureteral sphincter, but the oblique design of the entry of the ureter is perfect “structure and function” When the bladder fills up, the openings close When the bladder is empty, the openings are wide open

Question 39

Detail the 3 layers of the ureteral wall

Answer 39

Mucosa - Transitional epithelium - Lamina propria - No muscular mucosae Muscularis - “Circular” sandwich. Two longitudinal sandwiching a circular layer Adventitia - Serves to anchor the ureters into the surrounding C.T. structures

Question 40

Give a general overview of the anatomical structure of the urinary bladder, and the 3 layers of its wall, focusing on the uniqueness of its epithelium

Answer 40

- In males, it lies medially and directly anterior to the rectum. Sits superior to the pubic - In females, it lies medially and superior to the pubis. It’s directly anterior to the vagina and inferior to the uterus. Mucosa Transitional epithelium. The deepest layer is cuboidal when empty and transitions to simple squamous when filling Muscularis “Circular” sandwich. Middle circular rivers ruin around the opening out of the bladder to form the internal ureteral sphincter Adventitial Anchoring to the surrounding C.T.

Question 41

Contrast the female and male urethra, describing the internal and external urethral sphincters, external urethral orifices, and the 3 parts to the male urethra

Answer 41

Females: - The external urethral openings lie posterior to the clitoris and anterior to the vaginal opening - Mucosa is transitional epithelium nearest the bladder, then stratified columnar/pseudostratified columnar as it moves distally, then near the external urethral orfices, it becomes non-keratinized stratified squamous Males: Overall length and travel of the urethra is much different and has 3 sections: - Prostatic runs through the prostate - Membranous is a very short segment connectin prostatic and spongy - Spongy runs through the length of the penis - Mostly circular smooth muscle in the prostatic urethra, helping form the internal urethral sphincter - In the membranous urethra, the circular fibers become skeletal through the deep muscles of the perineum, forming the external urethral sphincter

Question 42

Describe the micturition reflex, contrasting it in infants vs. continent children and adults

Answer 42

Micturition reflex will trigger voiding the bladder automatically when the bladder begins to fill Unless you learn (via cerebral cortex) to control the external urethral sphincter, and relax and contract involuntarily to initiate urination or demand or delay it voluntarily.

Question 43

Describe the epithelium of each section of the renal tubule, correlating each epithelium to a brief overview of the major reabsorptive/secretory function of each section

Answer 43

Glomerulus = highly modified simple squamous epithelium. Site of filtration, so looking for the thinnest epithelium possible Proximal convoluted tubule (PCT) = simple cuboidal epithelium with apical microvilli. Lots of sections and reabsorption early on in the tubule so looking for tons of surface area. Descending loop of Henle and thin ascending loop = simple squamous epithelium. Less secretion and absorption, here, and structurally, the tubules are thin Thick ascending loop of Henle = simple cuboidal to “low” columnar epithelium. More secretion and absorption, here, so looking for more “powerful” cells Distal convoluted tubule (DCT): More proximal stretches = simple cuboidal epithelium. Moderate amount of secretion and absorption Most distal stretches, and extending into collecting ducts = intercalated (pH modifying) and principal cells (ADH and Aldosterone sensitive). Looking for ADH and aldosterone sensitivity and pH-modifying cells