Lecture 16: Micturition and Glomerular Filtration Flashcards
Describe the Micturition Reflex
See Slide 4
- Superimposed micturition contractions begin to appear as bladder fills.
- Sensory signals from bladder stretch receptors:
- Conducted to sacral region of spinal cord via pelvic nerves
- Conducted reflexively back to bladder via parasympathetic nerves
- Reflex contractions relax spontaneously when bladder is only partially filled.
- Once initiated, the micturition is self-regenerative.
- The self-regenerative reflex fatigues after a few seconds and the bladder relaxes.
- As bladder continues to fill, micturition reflexes occur more often and are more powerful.
- When micturition reflex is powerful enough, it causes a second reflex:
- Passes through pudendal nerves to inhibit external sphincter.
- Higher brain centers (in pons) keep micturition partially inhibited except when micturition is desired.
- When it is time to urinate, the cortical centers can facilitate the sacral micturition centers to help initiate a micturition reflex and at the same time inhibit the external urinary sphincter so that urination can occur.
- See Slide 7-9
Describe the function of nephrons
- Get rid of waste materials:
- Urea, creatinine, uric acid, bilirubin
- Regulate water and electrolyte balance
- Regulate body fluid osmolarity
- Regulate arterial pressure:
- Long term:
- Excrete variable amounts of sodium ion and water
- Short term:
- Secrete hormones and vasoactive factors such as renin
- Regulate acid-base balance:
- Excrete acids and regulate body fluid buffer stores
- Eliminate sulfuric and phosphoric acids (from protein metabolism)
- Secretion, metabolism, and excretion of hormones:
- Erythropoietin
- Active form of vitamin D 12
- Gluconeogenesis
Describe the three processes that determine the rates at which different substances are excreted in the urine
- Filtration
- Reabsorption
- Secretion
Know the mathematical expression of the urinary excretion rate
Urinary Excretion Rate =
Filtration Rate ─ Reabsorpon Rate + Secretion Rate
- See Slide 14-17
Describe Filtration
Filtration is the first step in urine formation. Components of the glomerular filtrate:
- Water
- Ions
- Glucose
- Urea
Filtration fraction = GFR/Renal plasma flow
- Fraction of renal plasma flow that is filtered ≈ 0.2 (i.e., 20% of plasma flowing through kidney is filtered.)
- Concentration of most substances except for proteins is the same in the filtrate and the plasma.
- Some low-molecular weight substances are not freely filtered because they are partially bound to proteins.
See Slide 22
What are the three layers of the filtration barrier?
- Endothelium
- With fenestrae and negative charges
- Basement membrane
- With collagen and proteoglycan fibers and strong negative charges
- Podocytes
- With negative charges
Describe the glomeruler filtration rate (GFR)
- Determined by:
- Balance of hydrostatic and colloid osmotic forces acting across capillary membrane
- Capillary filtration coefficient
– Product of permeability and filtering surface area of capillaries (K1)
8 GFR = 125 ml/min = 180 L/day - Water has a filterability of 1.0.
- Albumin molecules (6 nm) are slightly smaller than the filtration pores (8 nm) but have negative charges.
- What are some of the diseases that lower glomerular capillary filtration coefficient?
- Define minimal change nephropathy
- Define hydronephrosis
- Chronic uncontrolled hypertension and diabetes mellitus
- Loss of negative charges on the basement membrane
- Distension and dilation of renal pelvis and calyces
What is the glomerular filtration rate equation?
GFR = K1x Net filtration pressure:
GFR = K1x (Pg− Pb− πg+ πb)
- Pg= glomerular hydrostatic pressure = 60 mm Hg
- Pb= Bowman’s capsule hydrostatic pressure = 18 mm Hg
- πg= glomerular capillary colloid osmotic pressure = 32 mm Hg
- πb= colloid osmotic pressure of Bowman’s capsule = 0
K1 = Capillary filtration coefficient
= Product of permeability and filtering surface area of capillaries
So GFR would equal 10.
K1 = GFR/Net filtration pressure
What does raising and lowering the K1 do to the GFR
- Raising K1 raises GFR
- Lowering K1 lowers GFR
- Factors that influence glomerular capillary colloid osmotic pressure:
- Arterial plasma colloid osmotic pressure
- Filtration fraction Factors that increase glomerular colloid osmotic pressure:
- Increasing filtration fraction
What are variables that determine glomerular hydrostatic pressure
- Arterial pressure:
- Increase → ↑PG→ ↑GFR
- Afferent arteriolar resistance:
- Increase → ↓PG→ ↓ GFR
- Efferent arteriolar resistance:
- Increase → ↑PG→ ↑ GFR (slightly)
List factors that determine renal blood flow
What is the renal blood flow formula?
- Kidneys have 7X the blood flow of the brain but only 2X the oxygen consumption of the brain.
- Much of the oxygen consumed by the kidneys is related to the high rate of active sodium reabsorption.
- Tubular sodium reabsorption is closely related to GFR and rate of sodium filtered.
Renal Blood Flow = (Renal artery pressure − Renal vein pressure)/(Total vascular resistance)
Describe nervous regulation of GFR
- All blood vessels of the kidney are richly innervated by sympathetic system.
- Strong activation of renal sympathetic nerves:
- Constrict renal arterioles
- Decrease renal blood flow and GFR
- Moderate sympathetic activation has little effect.
List mechanisms controlling GFR consistency
- Sympathetic system (see above)
- Hormones:
- Norepinephrine and epinephrine (from adrenal medulla):
- Parallel the sympathetic system
- Endothelin:
- Angiotensin II:
- Endothelial-derived NO
- Prostaglandins and bradykinin
Describe the role of endothelin in controlling GFR
- Released by damaged vascular endothelial cells of the kidneys and other tissues.
- May contribute to renal vasoconstriction leading to reduced GFR
- May contribute to hemostasis when a blood vessel is severed.
- Plasma levels increase in certain disease states associated with vascular injury:
- Toxemia of pregnancy
- Acute renal failure
- Chronic uremia
Describe the role of Angiotensin II in controlling GFR
- Preferentially constricts efferent arterioles
- Formed usually in situations associated with decreased arterial pressure or volume depletion.
- Effects on the efferent arterioles will help to increase GFR
- Afferent arterioles seem to be protected against the effects of angiotensin II.
- Due to release of prostaglandins and nitric oxide which are vasodilators
Describe the role of nitric oxide in controlling GFR
- Derived from endothelial cells
- Basic level helps maintain renal vasodilation
Describe the role of bradykinin and prostaglandins in GFR
- Vasodilators that may offset effects of sympathetic and angiotensin II vasoconstrictor effects (esp. on afferent arterioles)
Describe Autoregulation
- Autoregulation refers to the relative constancy of GFR and renal blood flow.
- Primary function is to:
- Maintain a relatively constant GFR
- Allow precise control of renal excretion of water and solutes.
- Prevent relatively large changes in GFR and renal excretion that would otherwise occur with changes in blood pressure.
- Normal GFR = 180 L/day
- Tubular reabsorption = 178.5 L/day
Therefore: - Normal daily fluid excretion = 1.5 L/day
Without autoregulation, a slight increase in blood pressure could increase GFR up to 225 L/day. - This would increase urine flow to 46.5 L/day.
Describe the tuberoglomerular feedback system and the juxtaglomerular complex
- Tubuloglomerular feedback mechanism for autoregulation:
- Two components:
- An afferent arteriolar feedback mechanism
- An efferent arteriolar feedback mechanism
- Juxtaglomerular complex:
- Macula densain distal tubule
- Juxtaglomerular cells in afferent and efferent arterioles
- See Slide 42
More specifically explain autoregulation in the JG complex
- ↓GFR → slow flow rate in loop of Henle →:
- ↑reabsorpon of sodium and chloride ions in the ascending limb
- ↓ in sodium chloride at macula densa
- ↓in [NaCl] results in a signal from macula densa →:
- ↓resistance to blood in afferent arterioles
- ↑ renin release from JG cells (major storage site of renin)
- ↑angiotensin II
- ↑efferent arteriolar resistance
- See slide 44-45