Lecture 4 : Regulation of the Nephron Flashcards
The end of the tubule is where we regulate _____ to “fine tune” filtrate to the needs of the body
absorption and secretion
At the DCT and Collecting Duct:
Make urine more dilute or more concentrated than blood
Change ion concentrations further
Adjust pH
Cells of the Distal Convoluted Tubule
Perform only small amounts of absorption and secretion
Simple cuboidal cells but lighter staining
Cells of the Distal Convoluted Tubule functions:
fewer mitochondria needed for less active transport
Few or no microvilli on apical surface
> Need fewer transport proteins here
__________ play a major role in the
fine tuning of urine
Collecting Ducts
Note that collecting ducts pass all the way through the medulla to the _____ – they use the osmotic gradient to adjust final water content in the urine
renal papilla
The Collecting Ducts receive filtrate from many nephrons and release urine into the ______
minor calyx
The collecting duct receives filtrate from nephrons in the renal cortex and contains two cell types:
Principal cells – maintain body’s water and sodium balance
Intercalated cells – maintain the acid-base balance in blood
Near the papilla, collecting ducts fuse into papillary ducts with _______
columnar epithelium
Once the fluid reaches the end of the papillary duct it is officially called ___ because the processing is done
urine
We get feedback from the fluid in the early DCT
key area for “sampling” filtrate
The Distal Convoluted Tubule Passes between the Afferent and Efferent Arterioles at the ____
Glomerulus
The ________ is a “sensor” region that monitors filtrate formation and blood pressure
juxtaglomerular apparatus
JGA consists of 3 types of cells that help regulate rate of filtrate formation and systemic blood pressure. These cells respond to Na levels in filtrate and blood pressure by making adjustments to GFR.
mascula densa
granular cells
Extraglomerular mesangial cells
Macula densa
(dense spot): cells with chemoreceptors that monitor NaCl content in the filtrate of DCT
Granular cells (JG or Juxtaglomerular cells):
specialized smooth muscle cells that act as mechanoreceptors sensing blood pressure in afferent arteriole
Granular cells release the enzyme ___ if needed
renin
Extraglomerular mesangial cells
can pass regulatory signals between macula densa and granular cells
Outward (out of capillary) pressures ____ filtrate formation:
PROMOTE
Hydrostatic pressure in glomerular capillary (HPgc)
Glomerular capillary pressure
Higher than normal capillary pressure to ensure filtration across whole length
Inward (into capillary) pressures _____ filtrate formation:
OPPOSE
Hydrostatic pressure in the capsular space (HPcs)
Pressure exerted by filtrate in the glomerular capsule
Colloid osmotic pressure in glomerular capillary (OPgc)
Pressure exerted by proteins in the blood drawing water toward them
A ____ Net Filtration Pressure (NFP) = Filtrate Formation
POSITIVE
_______ is the volume of filtrate/minute formed by all glomeruli in the kidneys
Glomerular Filtration Rate (GFR)
Glomerular Filtration Rate (GFR) is directly proportional to:
- Net Filtration Pressure (NFP)
- Surface area of all glomeruli
- Filtration membrane permeability
Net Filtration Pressure (NFP)
NFP = HPgc – (HPcs + OPgc)
Main controllable factor
Glomerular hydrostatic pressure (HPgc) biggest influence – change diameter of arterioles
Changing capillary hydrostatic pressure commonly impacts NFP and therefore ___
GFR
Disease processes can affect number of _____ or integrity of filtration membrane
glomeruli (surface area)
Glomerular Filtration Rate is Closely Tied to ___
Homeostasis
Kidneys need constant ___ to make filtrate and maintain extracellular homeostasis
GFR
If GFR increases:
more filtrate is formed and urine output increases
Filtrate moves quickly through tubule and substances that would normally be reabsorbed are partially lost in urine (ions, water)
Ion imbalances can result
Blood volume and blood pressure decrease (because water is excreted)
If GFR decreases:
less filtrate is formed and urine output decreases
Filtrate moves slowly through tubule and there is more time for reabsorption
Some wastes normally lost in urine are reabsorbed into blood
Blood volume and blood pressure increase (because more water is conserved)
Two Types of Control Mechanisms Regulate GFR
Intrinsic controls
Extrinsic controls
Intrinsic controls (also called renal autoregulation)
act locally within the kidney to maintain GFR despite changes in systemic blood pressure
– changes are minute to minute in response to normal fluctuating changes in blood pressure – allow kidney “to do its job”
Myogenic mechanism
Tubuloglomerular feedback mechanism
Extrinsic controls
under extreme conditions in which blood pressure falls outside normal range (i.e. hypovolemic shock)
nervous system and endocrine (hormonal) systems kick in to maintain systemic blood pressure and preserve blood flow to brain & vital organs
Nervous regulation : sympathetic nervous system
Hormonal regulation : Renin-Angiotensin-Aldosterone Mechanism (RAAS)
Adjustments to _________ are the easiest way to impact NFP and therefore GFR
glomerular capillary hydrostatic pressure
Intrinsic Control of GFR (Renal Autoregulation):
Myogenic Mechanism
Myogenic Mechanism
Smooth muscle reflexively contracts when stretched & relaxes when not stretched – inherent property of smooth muscle
Increased systemic blood pressure stretches afferent arteriole causing reflexive smooth muscle contraction – blood flow into glomerulus ↓ preventing GFR ↑
Intrinsic Control of GFR (Renal Autoregulation):
Tubuloglomerular Feedback Mechanism
Tubuloglomerular Feedback Mechanism
Directed by the macula densa cells in the juxtaglomerular apparatus
Macula densa cells are sensitive to filtrate NaCl concentration in the ascending limb of loop
When GFR increases, time to reabsorb NaCl goes down, and the concentration of NaCl in the ascending limb of loop goes up
Macula densa cells release vasoconstrictor chemicals =
constricting the afferent arteriole
Glomerular hydrostatic pressure decreases and GFR is decreased =
allows more time for NaCl reabsorption
The two autoregulatory controls keep GFR relatively constant for blood pressure between =
80 – 180 mm Hg accounting for normal behavior (sleep, posture change, exercise)
Extrinsic Control of GFR : Sympathetic Nervous System
Driven by more extreme changes in SYSTEMIC blood pressure which alter baroreceptor activity
Norepinephrine from sympathetic nerve fibers
Epinephrine from adrenal medulla
Afferent arteriole constriction leads to a decreased GFR
conserves water, increases systemic BP
Sympathetic drive will damage the ___ to save the brain (if GFR decreased too much, too long)
kidney
Extrinsic Control of GFR :
Renin-Angiotensin-Aldosterone System (RAAS)
Stimuli that cause granular cells of JGA to release renin:
Macula densa cells sense low NaCl in filtrate, and signal granular cells to release renin
Granular cells detect reduced blood pressure in afferent arteriole and release renin
Sympathetic nerves trigger renin release from granular cells
Renin works as a blood enzyme converting inactive Angiotensinogen to _____
Angiotensin I
Angiotensin I is converted by Angiotensin Converting Enzyme (ACE) to ______
Angiotensin II
Effects of Angiotensin II :
Vasoconstriction
Stimulation of Aldosterone Release
Stimulates Na+/Cl- absorption at PCT
Stimulates thirst
____is major mechanism to increase blood volume and blood pressure
RAAS
Intrinsic Controls:
regulate GFR during moderate changes in blood pressure – minute to minute adjustmentsn
Extrinsic Controls:
indirectly regulate GFR by maintaining systemic blood pressure in emergency situations
There are no known receptors that monitor ____ in body fluids
Na+ levels
____is linked to blood pressure and blood volume control mechanisms
Sodium-water balance
Changes in blood pressure or volume trigger _____ controls to regulate Na+ content
neural and hormonal
Concentration of Na+ :
determines osmolality of ECF and influences excitability of neurons and muscles ; remains stable because of water shifts out of or into cells (shrinkage/swelling of cells)
Content of Na+ :
total body Na+ content determines ECF volume and therefore blood pressure
Three Hormones affecting Blood Pressure and Volume:
Aldosterone – reabsorbs Na so increases blood volume and blood pressure
Antidiuretic Hormone (ADH) – reabsorbs water so decreases ECF osmolality
Atrial Natriuretic Peptide (ANP) – decreases blood pressure and blood volume; suppress release of ADH, aldosterone, renin
Aldosterone Actions at Kidney
Triggers for release from adrenal cortex:
renin-angiotensin-aldosterone mechanism (RAAS) mediated by JGA of nephron
elevated K concentration in ECF
Aldosterone Results
Result: increased reabsorption of Na and secretion of K.
Aldosterone effects take hours
Aldosterone allows cells in the collecting duct to:
reabsorb sodium from tubule and return it to the blood
Synthesis of new sodium channels and insertion into apical surface of collecting duct cells
Diffusion of sodium through these channels is driven by _____ on _____
Na+/K+ pump
basal surface
Antidiuretic Hormone Actions at Kidney
ADH=Vasopressin
Diuretic –
increases urine production and therefore water excretion
Antidiuretic –
decreases urine production so conserves water
3 triggers for ADH release:
high blood osmolarity (dehydration)
low blood pressure
low blood volume
ADH increases aquaporin (water channel) insertion into collecting duct cells → _________
water reabsorption
Result: more concentrated urine (and increased blood volume)
ADH causes insertion of _____ into cells cells in the collecting duct
aquaporin proteins
Producing Dilute Urine
Water is not reabsorbed from the collecting duct – it stays in the filtrate.
Large amount of dilute urine is produced and excreted because we want to get rid of excess water.
When we are overhydrated:
↓ Osmolality of extracellular fluids
↓ ADH release from posterior pituitary
For dilute urine:
No ______ in collecting duct cells
aquaporins
Producing Concentrated Urine:
Water is reabsorbed from collecting duct (into vasa recta capillaries).
Small amount of concentrated urine is produced because we want to conserve water.
For concentrated urine:
Aquaporins are inserted into _____ of collecting duct cells
apical membranes
When we are dehydrated:
↑ Osmolality of extracellular fluids
↑ ADH release from posterior pituitary
The _______ in Necessary for Concentrating Urine
Renal Osmotic Gradient
Without the osmotic gradient, we would never be able to concentrate urine over _____
300 mOsm
Role of ADH:
ADH determines whether water can be reabsorbed by inserting aquaporins in the collecting duct cells
Role of Urea
waste product, but is a solute that aids in formation of osmotic gradient. Urea “cycles” between collecting duct, interstitium, and ascending loop
Role of Diuretics – increase urine output:
Alcohol – decreases ADH release
Caffeine – increases GFR, decreases Na reabsorption
Loop diuretics – inhibit formation of osmotic gradient by inhibiting pumps in ascending limb
Other drugs inhibit Na & water reabsorption
Intake of Water is Regulated by _____
Hypothalamus
Dehydration leads to:
↑ osmolality in ECF which stimulates _____ in hypothalamus
thirst centers
Decreased plasma volume
Stimulates renin-angiotensin-aldosterone system
stimulates thirst centers in hypothalamus
