LECTURE 10 (Urine formation by kidneys)

Question 1

What are the different functions of the kidneys?

Answer 1

• Excretion of metabolic waste products + foreign chemicals
  [urea, creatinine, uric acid, bilirubin, metabolites of various hormones]
• Regulation of water + electrolyte balances
  [for homeostasis + to alter ECF volume only SLIGHTLY]
• Regulation of body fluid osmolality + electrolyte concentrations
• Regulation of arterial pressure
  [excrete Na2+ and H2O + hormones and vasoactive factors/substances]
• Regulation of acid-base balance
  [excrete acids + regulate body fluid buffer stores]
• Secretion, metabolism + excretion of hormones
  [ERYTHROPOEITIN for production of RBC by hematopoetic stem cells + production of 1-25-dihydroxyvitamin D3 (CALCITRIOL) which is essential for Ca2+ deposition in bone and reabsorption by GI tract]
• Gluconeogenesis
  [synthesise glucose from amino acids during prolonged fasting]

Question 2

Describe the anatomy of the kidneys

Answer 2

• Two kidneys lie on posterior wall of abdomen outside peritoneal cavity
• Medial side -> HILIUM (renal artery + vein, lymphatics, nerve supply + ureter pass through)
• Outer cortex + inner medulla
  [Inner medulla -> separated into 8-10 renal pyramids]
• Base of each pyramid is from border between cortex and medulla + terminates in PAPILLA which projects into RENAL PELVIS
• Outer border is divided into open-ended pouches called “MAJOR CALYCES” which divide into “MINOR CALYCES” (collects urine from each papilla)

Question 3

Describe the Renal blood supply

Answer 3

Renal artery branches into:
- Interlobar arteries
- Arcuate arteries
- Interlobular arteries/Radial arteries
- Afferent arterioles
which lead to Glomerular capillaries

Distal ends of capillaries coalesce to form the EFFERENT ARTERIOLE which form PERITUBULAR CAPILLARIES around renal tubules -> Efferent arteriole separates the two capillary beds + regulates hydrostatic pressure in both -> High hydrostatic pressure in Glomerular capillaries cause FILTRATION + low hydrostatic pressure in Peritubular capillaries causes REABSORPTION -> Peritubular capillaries empty into: Interlobular vein, Arcuate vein, Interlobular vein, Renal vein

Question 4

Describe the Nephron

Answer 4

1) Glomerular capillaries (where large amounts of fluid filtered from blood) encased in BOWMAN’S CAPSULE -> fluid flows into Bowman’s capsule then into PROXIMAL TUBULE (lies in cortex of kidney)
2) Fluid flows into LOOP OF HENLE (dips into renal medulla) consisting of descending + ascending limb -> descending limb and lower end of ascending limb is “thin segment of loop of Henle” + ascending limb is “thick segment of ascending limb” (back to cortex)
3) Fluid flows to MACULA DENSA then into DISTAL TUBULE (lies in cortex) -> CONNECTING TUBULE -> CORTICAL COLLECTING TUBULE -> CORTICAL COLLECTING DUCT
4) 8-10 Cortical collecting ducts run into medulla becoming the MEDULLARY COLLECTING DUCT -> merge to form RENAL PAPILLAE

Question 5

What is the difference between Cortical and Juxtamedullary Nephrons?

Answer 5

Cortical nephrons (glomeruli located in outer cortex) = Short loops of Henle that penetrate a short distance into the medulla + entire tubular system is surrounded by PERITUBULAR CAPILLARIES

Juxtamedullary nephrons (glomeruli deep in renal cortex near medulla) = Long loops of Henle that dip deeply into medulla + long efferent arterioles extend from from glomeruli into outer medulla forming “VASA RECTA” (return towards cortex + empty into cortical veins)

Question 6

What happens in Micturition/Urination?

Answer 6

1) Bladder fills progressively until tension in walls rises above a threshold
2) Micturition reflex empties bladder/causes desire to urinate -> An autonomic spinal cord reflex but can be inhibited/facilitated by enters in cerebral cortex/brain stem

Question 7

Describe the anatomy of the bladder

Answer 7

• Body where urine collects + neck which passes inferiorly and anteriorly into UROGENITAL TRIANGLE and connects with urethra
• DETRUSOR MUSCLE -> contracts to empty bladder
  [smooth muscle cells fuse so action potential can spread causing unison contraction]
• On posterior wall of bladder -> “TRIGONE”
  [lower apex is the bladder neck which opens into POSTERIOR URETHRA + uppermost apex are two URETHRAL OPENINGS; Trigone mucosa is smooth compared to rest of bladder folded into “RUGAE”
• Bladder neck composed of detrusor muscle + elastic tissue -> “INTERNAL SPHINCTER” (smooth muscle)
• Urethra passes through UROGENITAL DIAPHRAGM containing “EXTERNAL SPHINCTER OF BLADDER” (skeletal muscle)

Question 8

Describe the innervation of the bladder

Answer 8

• PELVIC NERVES connect the spinal cord through the SACRAL PLEXUS (S2 and S3)
• Sensory fibers = detect degree of stretch in bladder wall
  [stretch signals from posterior urethra initiate bladder emptying]
• Parasympathetic fibers/Motor nerves = terminate on ganglion cells in wall of bladder -> short post-ganglionic nerves then innervate the detrusor muscle
• SKELETAL MOTOR FIBERS transmitted through PUDENDAL NERVE to external bladder sphincter -> somatic nerve fibers that control skeletal muscle of sphincter
• Sympathetic innervation from sympathetic chain through the HYPOGASTRIC NERVES -> connecting mainly with L2

Question 9

Describe the transport of urine from the Kidney into the bladder

Answer 9

• Urine flowing from the collecting ducts into the renal calyces stretches the calyces + increases pacemaker activity -> initiates peristaltic contractions that spread to RENAL PELVIS + downward along length of ureter -> force urine from renal pelvis towards the bladder
• Peristaltic contractions in ureter are enhanced by parasympathetic stimulation and inhibited by sympathetic stimulation
• DETRUSOR MUSCLE compresses ureter preventing back flow of urine when pressure builds up in bladder -> each peristaltic wave along ureter increases the pressure within ureter so region passing through bladder opens + allows urine to flow into bladder

Question 10

What is Vesicoureteral reflux?

Answer 10

When the distance that the ureter courses through the bladder wall is less than normal so contractions of bladder during micturition does not always lead to complete occlusion of ureter -> Urine in bladder is propelled backwards into ureter

MANIFESTATIONS:
- enlargement of ureters
- increase pressures in renal medulla + calyces

Question 11

What is the Ureterorenal reflex?

Answer 11

When a ureter becomes blocked, intense reflex constriction occurs + severe pain -> pain causes sympathetic reflex back to kidney to constrict renal arterioles -> decreases urine output from kidney

EXPLANATION: prevents excessive flow of fluid into the pelvis of a kidney with a blocked ureter

Question 12

What happens in the Micturition reflex?

Answer 12

1) Progressive and rapid increase of pressure
2) A period of sustained pressure
3) Return of the pressure to the basal tone of bladder

MICTURITION CONTRACTIONS “dashed spikes” appear as a result of stretch reflex by sensory street receptors on bladder wall -> Sensory signals conducted to SACRAL SEGMENTS of cord via PELVIC NERVES then back to bladder through the PARASYMPATHETIC NERVE FIBERS -> when bladder is partially filled, micturition contractions relax spontaneously but become more frequent + greater when filling again -> once reflex is powerful enough, another reflex passes through PUDENDAL NERVES to the EXTERNAL SPHINCTER to inhibit it -> If inhibition is greater in brain than voluntary constrictor signals to external sphincter, urination will occur

Question 13

How do the higher centers in the brain control micturition?

Answer 13

• Keep micturition reflex partially inhibited, except when micturition is desired
• Can prevent micturition, even if micturition reflex occurs, by tonic contraction of external bladder sphincter until a convenient time
• When it is time to urinate, cortical centers facilitate the sacral micturition enters to help initiate a micturition reflex + inhibit external urinary sphincter so that urination can occur

Question 14

What happens if the sensory nerve fibers are destroyed?

Answer 14

Overflow incontinence

EXPLANATION:
Micturition reflex cannot occur if sensory nerve fibers from bladder to spinal cord are destroyed, preventing transmission of stretch signals from bladder -> Instead of emptying periodically, bladder fills to capacity + overflows a few drops at a time through the urethra

COMMON CAUSE:
Crush injury to the sacral region of the spinal cord

Question 15

What happens if there is spinal cord damage above the sacral region?

Answer 15

Micturition reflexes can still occur but are no longer controlled by the brain

During the first few days/weeks reflexes are suppressed due to “spinal shock” -> but, if bladder is emptied periodically by catheterisation to prevent bladder injury by overstretching of bladder -> excitability of micturition reflex gradually increases until micturition reflexes return -> some patients control urination by stimulating the skin in genital region

Question 16

What happens if there is lack of inhibitory signals from the brain?

Answer 16

Frequent urination due to uncontrolled micturition reflex

EXPLANATION:
Partial damage in spinal cord/brain cell interrupts inhibitory signals from brain -> frequent + relatively uncontrolled micturition

Question 17

What are the three renal processes that determine the rates at which different substances are excreted in the urine?

Answer 17

1) Glomerular filtration
2) Reabsorption of substances from the renal tubules into the blood
3) Secretion of substances from the blood into the renal tubules

Question 18

What is the equation for Urinary excretion rate?

Answer 18

Urinary excretion rate = Filtration rate - Reabsorption rate + Secretion rate

Question 19

What is the filtration, reabsorption and secretion of different substances?

Answer 19

• End products of metabolism, urea, creatinine, uric acid, drugs = excretion rate is high + poorly reabsorbed
• Electrolytes = highly reabsorbed + small amounts in urine
• Nutritional substances, amino acids, glucose = completely reabsorbed + do not appear in urine

Question 20

Why are large amounts of solutes filtered and then reabsorbed by the kidneys?

Answer 20

• High GFR allows kidneys to rapidly remove waste products from the body that depend mainly on glomerular filtration for excretion
• High GFR allows all body fluids to be filtered + processed by kidneys many times each day
• High GFR allows kidneys to precisely + rapidly control the volume and composition of body fluids

Question 21

Describe Glomerular filtration

Answer 21

• The first step in urine formation
• Glomerular capillaries are relatively impermeable to proteins -> glomerular filtrate is “protein free” + goes into Bowman’s capsule
• GFR is determined by balance of hydrostatic and colloid osmotic forces acting across capillary membrane + CAPILLARY FILTRATION COEFFICIENT (product of permeability + surface area of capillaries)
  [High rate of filtration bc high glomerular hydrostatic pressure + large Kf]
• Filtration fraction = GFR/Renal plasma flow

Question 22

Describe the Glomerular capillary membrane

Answer 22

• Contains endothelium, basement membrane and a layer of epithelial cells (podocytes)
• FUNCTION: prevents filtration of plasma proteins + large negatively charged ions
• Endothelium = perforated by thousands of “fenestrae” + fixed negative charge
• Basement membrane = collagen + proteoglycan fibrillae that have large spaces through which large amounts of water + small solutes can filter
• Podocytes = separated by “slit pores” where glomerular filtrate moves + negative charge

[Glomerular capillary membrane is thicker than other capillaries BUT is more porous -> filters fluid at high rate]

Question 23

What determines the GFR?

Answer 23

• Sum of hydrostatic and colloid osmotic forces across the glomerular membrane which gives the “net filtration pressure”
• Glomerular filtration coefficient (Kf)

GFR = Kf X Net filtration pressure

GFR=Kf X(PG -PB -πG +πB)
[PG = glomerular hydrostatic pressure which promotes filtration, PB = hydrostatic pressure in Bowman’s capsule which opposes filtration, πG = glomerular colloid osmotic pressure which opposes filtration, πB = Bowman’s colloid osmotic pressure which promotes filtration]

Question 24

What is Kf?

Answer 24

A measure of the product of the hydraulic conductivity + surface area of capillaries

CLINICAL CORRELATION:
Increased glomerular capillary filtration coefficient increases GFR

Question 25

What can decrease the GFR?

Answer 25

• Increasing Bowman’s capsule hydrostatic pressure
  [can be caused by urinary stones + can cause hydronephrosis and damage kidney]
• Increased Glomerular capillary colloid osmotic pressure
  [caused by arterial plasma colloid osmotic pressure + fraction of plasma filtered by glomerular capillaries “filtration fraction”]

Question 26

What determines Glomerular hydrostatic pressure?

Answer 26

• Arterial pressure
  [Increased arterial pressure -> increased hydrostatic pressure -> increase GFR]
• Afferent arteriolar resistance
  [Increased resistance -> reduces hydrostatic pressure -> decrease GFR]
• Efferent arteriolar resistance
  [Increases resistance to outflow from glomerular capillaries -> raises hydrostatic pressure -> GFR increases slightly]

Question 27

What happens if efferent arteriolar constriction is severe?

Answer 27

Filtration fraction + glomerular colloid osmotic pressure increase as efferent arteriolar resistance increases -> Rapid, non-linear increase in colloid osmotic pressure by the Donnan effect -> Colloid osmotic pressure greater than glomerular capillary hydrostatic pressure -> DECREASE in GFR

Question 28

What is the large amount of oxygen consumed by the kidneys related to?

Answer 28

The high rate of active sodium reabsorption by the renal tubules

EXPLANATION: If renal flow and GFR are reduced -> less sodium is filtered -> less sodium is reabsorbed and less oxygen is consumed

Question 29

How do you calculate Renal blood flow?

Answer 29

(Renal artery pressure - Renal vein pressure) / Total renal vascular resistance

[pressure gradient across the renal vasculature divided by total renal vasculature resistance -> If resistance increases, blood flow decreases]

Question 30

What has greater blood flow, Renal cortex or Renal medulla?

Answer 30

Renal cortex

EXPLANATION: Most of the kidney’s blood flow goes to the Cortex whereas 1-2% go to the “vasa recta” which supplies the medulla

Question 31

What effect does the Sympathetic nervous system have on the kidneys?

Answer 31

STRONG activation of the renal sympathetic nerves can constrict the renal arterioles and decrease renal blood flow and GFR

ADDITIONAL INFO: kidney nerves have most influence on blood flow + important for brain ischemia, severe haemorrhage

Question 32

What effect does Norepinephrine, Epinephrine and Endothelia have on the kidneys?

Answer 32

• Norepinephrine + Epinephrine = released by adrenal medulla + little influence on renal dynamics except for extreme conditions
• Endothelia = released by damages vascular endothelial cells + vasoconstrictor + contribute to homeostasis

ALL OF THEM constrict afferent and efferent arterioles -> reductions in GFR and renal blood flow

Question 33

What are the effects of Angiotensin II?

Answer 33

• Efferent arterioles (unlike afferent) are sensitive to Angiotensin II -> constriction prevents decreases in glomerular hydrostatic pressure + GFR (helps excretion of metabolic waste) whilst reducing renal blood flow (this increases reabsorption of sodium and water)
• Effect is called “Autoregulation”

Question 34

What is the effect of Endothelial-derived nitric oxide?

Answer 34

It decreases renal vascular resistance which increases GFR

CLINICAL CORRELATION:
Patients administered drugs that inhibit formation of nitric oxide increases renal vascular resistance, decreases GFR and urinary sodium excretion -> High BP

Question 35

What are the effects of Prostaglandins and Bradykinin?

Answer 35

Increase GFR

Prostaglandins (PGE2 and PGI2) and Bradykinin dampen vasoconstrictor effects of sympathetic nerves or angiotensin II and oppose vasoconstriction of afferent arterioles -> Increase GFR

Question 36

What is the major function of auto regulation in the kidneys?

Answer 36

To maintain a relatively constant GFR and allow precise control of renal excretion of water and solutes

Question 37

Why do changes in arterial pressure not have as much of an effect on urine volume?

Answer 37

• Renal auto regulation prevents large changes in GFR
• There are additional adaptive mechanisms in renal tubules that cause them to increase reabsorption rate when GFR rises “glomerulotubular balance”

Question 38

What is the Tubuloglomerular feedback mechanism?

Answer 38

An auto regulation mechanism that links changes in sodium chloride concentration at the macula densa with the Renal arteriolar resistance -> stabilises sodium chloride delivery to distal tubule

TWO COMPONENTS TO CONTROL GFR:
- afferent arteriole feedback mechanism
- efferent arteriolar feedback mechanism
BOTH mechanism depend on “Justaglomerular complex”

JUXTAGLOMERULAR COMPLEX consists of:
- “macula densa” cells in initial portion of distal tubule
- “juxtaglomerular cells” in walls of afferent and efferent arterioles

Question 39

What is the function of the Macula Densa?

Answer 39

Decreased macula densa sodium chloride causes dilation of afferent arterioles and increased renin release

Decreased GFR slows the flow rate in the loop of Henle -> causes increased reabsorption on Na2+ and Cl- in ascending loop of Henle -> reduces concentration of NaCl at macula densa cells -> Macula densa has two effects:
- Decreases resistance to blood flow in afferent arterioles -> raises glomerular hydrostatic pressure + increases GFR
- Increases Renin release from juxtaglomerular cells of afferent and efferent arterioles -> Increase formation of Angiotensin I which is converted to Angiotensin II -> constricts efferent arterioles to increase glomerular hydrostatic pressure + GFR

Question 40

What happens in Myogenic Autoregulation?

Answer 40

Arterioles respond to increased wall tension or wall stretch by contraction of vascular smooth muscle -> stretch increases Ca2+ from ECF into cells allowing for contraction -> raises vascular resistance which prevents excessive increases in renal blood flow and GFR when arterial pressure increases

Question 41

How does a high protein diet increase GFR?

Answer 41

1) A high protein meal increases the release of amino acids into the blood which is reabsorbed with Na2+ in the PROXIMAL TUBULES -> decreases sodium delivery to “macula densa”
2) Macula densa decrease afferent arterioles resistance which increases renal blood flow + GFR

SAME MECHANISM FOR INCREASE IN GLUCOSE!!