Exam 4 pt. 2

Question 1

Generally, how much filtrate is made each day? How much urine?

Answer 1

o ~180 L (47 gallons) of blood-derived filtrate is processed by the kidneys each day, only ~1.5L of urine is formed – less than 1%!
o The kidneys filter the body’s entire blood plasma volume 60x each day
o At rest, 20-25% of the body’s O2 supply is used by the kidneys

Question 2

Define filtrate

Answer 2

o Filtrate: blood plasma minus its proteins; produced by glomerular filtration

Question 3

Define urine

Answer 3

o Urine: metabolic wastes and unneeded substances; produced from filtrate

Question 4

List the 3 processes involved in urine formation. What happens in each process?

Answer 4

o Glomerular Filtration: produces cell and protein-free filtrate
o Tubular Reabsorption: process of selectively reclaiming substances from filtrate and moving them back into blood
 Typically, 99% of water, and all glucose and amino acids are reabsorbed
o Tubular Secretion: process of selectively moving substances from blood into filtrate

Question 5

What are the 3 layers of the filtration membrane?

Answer 5

o Fenestrated Endothelium of Glomerular Capillaries: allows all blood components except cells to pass
o Basement Membrane: allows solutes; blocks all but the smallest proteins
o Foot Processes of Podocytes of the Glomerular Capsule: filtration slits between foot processes, stop all remaining macromolecules

Question 6

Define the 3 pressures involved in glomerular filtration and have a general idea of their valves.

Answer 6

o Outward Pressures: forces that promote the formation of filtrate
o Hydrostatic Pressure in Glomerular Capillaries (HPgc) – essentially glomerular blood pressure
 Chief force pushing water, solutes out of blood across the filtration membrane
 Quite high (55mmHg) compared to most capillary beds
 Maintained by the smaller size of efferent arteriole versus the afferent arteriole
o Inward Pressures: forces that inhibit the formation of filtrate
o Hydrostatic Pressure in the Capsular Space (HPcs) – pressure exerted by the filtrate in the glomerular capsule (~15mmHg)
o Colloid Osmotic Pressure in Glomerular Capillaries (OPgc) – the “pull” of the proteins in the blood (~30mmHg)

Question 7

Define outward pressure

Answer 7

o Outward Pressures: forces that promote the formation of filtrate

Question 8

Define hydrostatic pressure in glomerular capillaries

Answer 8

o Hydrostatic Pressure in Glomerular Capillaries (HPgc) – essentially glomerular blood pressure
 Chief force pushing water, solutes out of blood across the filtration membrane
 Quite high (55mmHg) compared to most capillary beds
 Maintained by the smaller size of efferent arteriole versus the afferent arteriole

Question 9

Define inward pressures

Answer 9

o Inward Pressures: forces that inhibit the formation of filtrate

Question 10

Define hydrostatic pressure in capsular space

Answer 10

o Hydrostatic Pressure in the Capsular Space (HPcs) – pressure exerted by the filtrate in the glomerular capsule (~15mmHg)

Question 11

Define Colloid Osmotic Pressure in Glomerular Capillaries (OPgc)

Answer 11

o Colloid Osmotic Pressure in Glomerular Capillaries (OPgc) – the “pull” of the proteins in the blood (~30mmHg)

Question 12

Define NFP. Is it a net outward or inward force?

Answer 12

o Net Filtration Pressure (NFP): the sum of forces
 55mHg forcing out
 45mmHg forcing in
 Net: 10mmHg of outward force
o NFP is the pressure responsible for forming filtrate
o NFP is the main controllable factor for determining Glomerular Filtration Rate (GFR)

Question 13

What is GFR?

Answer 13

o GFR: the volume of filtrate formed by both kidneys per minute
o Normal GFR = 120 - 125 mL/min

Question 14

How is GFR used clinically? What 3 things determine GFR?

Answer 14

o GFR is directly proportional to:
 Net Filtration Pressure (NFP): main controllable factor, primary pressure is outward glomerular hydrostatic pressure, can be controlled by changing arteriole diameters
 Total surface area available for filtration – controlled by the contraction of mesangial cells
 Permeability of filtration membrane – much more permeable than other types of capillaries
o Large surface area and high permeability allow the relatively small NFP to produce huge amounts of filtrate

Question 15

In terms of GFR, what is normal for a healthy adult? What values are associated with CKD? With renal failure?

Question 16

Describe the relationship between GFR and systemic blood pressure.

Answer 16

o GFR is regulated to serve 2 important – and sometimes opposing – needs
o The kidneys need a relatively constant GFR to continue making filtrate
o The body needs a relatively constant blood pressure
o An increase in GFR increases urinary output and decreases BP
o A decrease in GFR decreases urinary output and increases BP

Question 17

What’s the difference between intrinsic and extrinsic controls?

Answer 17

o Intrinsic Controls: work locally within the kidney to maintain GFR – renal autoregulation
o Extrinsic Controls: neural and hormonal controls that maintain systemic blood pressure

Question 18

What is an appropriate MAP range for intrinsic controls to be in control?

Answer 18

o 80-180 mmHg

Question 19

Define myogenic mechanism. What happens when BP increases or decreases under myogenic mechanism?

Answer 19

o Myogenic Mechanism: smooth muscle contracts when stretched
 Increased BP -> Muscles Stretch -> Constriction of Afferent Arteriole
 Decreased BP -> Dilation of Afferent Arteriole
 Goals: protect the glomerulus from high BP by restricting blood flow, maintain normal NFP and GFR

Question 20

Define tubuloglomerular feedback mechanism. What group of cells directs this mechanism? What solute is driving this mechanism?

Answer 20

o Tubuloglomerular Feedback Mechanism: directed by the macula densa cells
 Responds to NaCl concentration
 GFR increases -> flow of filtrate increases -> decreased time for reabsorption -> higher levels of NaCl in filtrate
 Response: the afferent arteriole is constricted -> NFP and GFR are reduced -> increased time for NaCl reabsorption

Question 21

What systemic effects are seen in extrinsic neural control by the SNS? How does this alter BP?

Answer 21

o Extrinsic controls regulate GFR to maintain systemic BP – even if it hurts the kidneys!
o Ex: in the event of hypovolemia, extrinsic controls will override the intrinsic controls to ensure survival of the vital organs
o Neural Control by the Sympathetic Nervous System
 Normal Conditions: renal blood vessels are dilated, intrinsic controls running
 Abnormal Conditions (Low BP): norepinephrine, epinephrine are released
* Systemic vasoconstriction to raise BP
* Constriction of the afferent arterioles will decrease GFR
* Blood volume and blood pressure increase

Question 22

Outline how renin increases systemic blood pressure.

Answer 22

o Renin-Angiotensin-Aldosterone Mechanism
o The body’s main mechanism for increasing blood pressure
o 3 pathways to releasing renin from the granular cells
 Direct stimulation of granular cells by the SNS
 Simulation of the granular cells by activated macula densa cells – when NaCl concentration in filtrate is low
 Reduced stretch of granular cells
o Anuria: abnormally low urine output (< 50 mL/day); multiple causes

Question 23

What are some things that are reabsorbed in tubular reabsorption? Which portion of the renal tubule conducts the most reabsorption?

Answer 23

o Tubular reabsorption quickly reclaims most of the tubular contents and returns them to blood
o Tubular reabsorption is an elective transepithelial process. It starts as soon as filtrate enters the proximal tubule.
o Almost all organic nutrients are reabsorbed; reabsorption of water and ions is hormonally regulated and adjusted as needed
o Tubular reabsorption can be either active (ATP-requiring) or passive
o Two Routes:
 Transcellular: reabsorbed substances travel through cells of the tubule
 Paracellular: reabsorbed substances travel between cells of the tubule

Question 24

What is reabsorbed in the PCT?

Answer 24

 The PCT is the site of most reabsorption
 What is reabsorbed from the filtrate in the PCT?
* All the nutrients (glucose + amino acids)
* 65% of sodium + water
* Most of the electrolytes
* Nearly all uric acid and ~1/2 of the urea – these will be secreted into the filtrate again later!

Question 25

What is reabsorbed in the Nephron Loop?

Answer 25

 In the nephron loop, reabsorption of water is no longer coupled to solute reabsorption  Descending Limb: water can leave, but solute cannot  Ascending Limb: solute can leave, but water cannot

Question 26

What is reabsorbed in DCT?

Answer 26

 Reabsorption in the DCT varies with the body’s current needs – it is hormonally regulated  Most of the water and solutes have already been reabsorbed  Anti-Diuretic Hormone (ADH): released by the posterior pituitary gland, can cause an increase in reabsorption of water  Aldosterone: increases blood pressure and decreases K+ levels by promoting the reabsorption of Na+  Atrial Natriuretic Peptide (ANP): released by cardiac atrial cells, decreases blood volume and blood pressure by reducing the reabsorption of Na+  Parathyroid Hormone: increases reabsorption of Ca2+ by the DCT

Question 27

Refamiliarize yourself with ADH, aldosterone, ANP, and parathyroid hormone. What do each of these do?

Question 28

What is tubular secretion? Make a list of things typically secreted.

Answer 28

o Tubular secretion is the reverse of tubular reabsorption o Tubular secretion occurs almost entirely in the PCT o In secretion, selected substances are moved from the peritubular capillaries, through the tubule cells, and back into the filtrate o Things that are often secreted: K+, H+, Ammonia, Creatinine, Organic Acids and Bases o Tubular secretion is important for:  Disposing of substances – drugs and metabolites – that are bound to plasma proteins  Eliminating undesirable substances - urea and uric acid - that were passively reabsorbed  Ridding the body of excess K+ - the aldosterone effect  Controlling pH by altering amounts of H+ or HCO3- in urine

Question 29

What’s renal clearance?

Answer 29

o Renal Clearance: the volume of plasma that the kidneys can clear of a particular substance within a given time o Renal clearance tests can determine GFR, detect glomerular damage, and follow the progress of renal disease

Question 30

What are the treatment options for renal failure?

Answer 30

o Renal Failure: a GFR < 15 mL/min  Formation of filtrate dramatically decreases or completely stops  Uremia: “urine in the blood” – ionic and hormonal imbalances, metabolic abnormalities, toxic molecule accumulation  Symptoms: fatigue, anorexia, nausea, mental status changes, cramps  Treatment: hemodialysis or kidney transplant

Question 31

Be prepared to answer a question about what is “normal” or “abnormal” to be found in urine. And review the chart to recall what abnormal findings may indicate.

Answer 31

o Chemical Composition o 95% Water, 5% Solutes o Nitrogenous Wastes  Urea: largest solute component; formed from breakdown of amino acids  Uric Acid: product of nucleic acid metabolism  Creatinine: metabolite of creatine phosphate – found in large amounts in skeletal muscle o Normal Solutes in Urine: urea, Na+, K+, PO43-, SO42-, creatinine, uric acid  Ca2+, Mg2+, HCO3- are occasionally seen in small amounts o Abnormal Solutes in Urine: blood proteins, WBCs, and bile pigments – presence of these can indicate pathology

Question 32

Review the physical characteristics of urine (slide 25).

Answer 32

o Color and Transparency  Freshly voided urine is clear - pale to deep yellow  Urochrome: pigment that results from the body’s destruction of hemoglobin  More concentrated urine is deeper in color  Abnormal colors (pink, brown, red) can be caused by certain foods, medications, drugs, vitamins, and the presence of bile/blood  Cloudy urine may indicate a urinary tract infection (UTI) o Odor  Only slightly aromatic when fresh  Upon standing, develops an ammonia odor as bacteria metabolizes urea  May be altered by some drugs, foods, and diseases o pH  Slightly acidic (pH = ~6, range 4.5 to 8)  Acidic (high protein) or alkaline (vegetarian) diets will alter pH  Prolonged vomiting and UTIs can also raise pH o Specific Gravity  Ratio of the mass of a substance to the mass of an equal volume of distilled water  Urine’s specific gravity ranges from 1.001 to 1.035

Question 33

What’s the trigone of the bladder? What 3 openings form the trigone?

Answer 33

o Trigone: smooth triangular area outlined by the openings for the 2 ureters and the urethra o Ureters: slender tubes that actively carry urine away from the kidneys towards the bladder o Ureters are retroperitoneal continuations of the renal pelvis o Enter the base of the bladder – through the posterior wall o As bladder pressure increases, the distal ends of the ureters prevent backflow of urine into the ureters o Three Layers:  Mucosa  Muscularis: smooth muscle that contracts in response to stretch  Adventitia o Urethra: muscular tube that drains the urinary bladder o Mucosal lining is largely pseudostratified columnar epithelium – transitional epithelium near the bladder – stratified squamous near the external opening o Urethral Sphincters:  Internal Urethral Sphincter: involuntary/smooth muscle at the bladder-urethral junction – contracts to open  External Urethral Sphincter: voluntary/skeletal muscle surrounding the urethra as it passes the pelvic floor – relaxes to open

Question 34

Name the smooth muscle of the bladder.

Question 35

What is considered the “max capacity” of the bladder?

Answer 35

o When empty, the bladder collapses and rugae appear o During filling, the bladder expands and rises superiorly, but there is no significant rise in internal pressure o Moderately Full Bladder:  ~12 cm/5 in long  500mL/1 pint of urine o Max capacity is about 1,000mL – an overfilled bladder can burst!

Question 36

Compare/contrast the male and female urethras.

Answer 36

o Female  3-4 cm/1.5 in long  Tightly bound to the anterior vaginal wall  External urethral orifice is anterior to the vaginal orifice o Male  Carries both semen and urine  Much longer – 20 cm/8 in - has 3 named regions * Prostatic Urethra: (2.5 cm) within prostate gland * Intermediate/Membranous Urethra: (2 cm) passes through urogenital diaphragm from prostate to root of penis * Spongy Urethra: (15 cm) passes through the penis, opens via external urethral orifice

Question 37

Where are the internal and external urethral sphincters located?

Answer 37

o Internal Urethral Sphincter: involuntary/smooth muscle at the bladder-urethral junction – contracts to open o External Urethral Sphincter: voluntary/skeletal muscle surrounding the urethra as it passes the pelvic floor – relaxes to open

Question 38

Outline the micturition reflex – as is done on slide 33! What sphincter relaxes to open? Which contracts? Which sphincter is autonomically controlled? Which is somatically controlled?

Answer 38

o Three Simultaneous Events  Contraction of the detrusor muscle by ANS  Opening of internal urethral sphincter by ANS * Opens via contraction!  Opening of external urethral sphincter by somatic nervous system * Opens via relaxation!