Section 6: Renal System Flashcards
External anatomy of kidneys
Renal capsule (innermost layer) Adipose capsule Renal fascia (outermost layer)
All made of CT - provides padding, protection and packaging
Kidneys: Renal capsule
Physical barrier; protection against trauma
Maintains shape of kidneys
Kidneys: Adipose capsule
Padding; physical protection
Maintains position of kidneys
Kidneys: Renal fascia
Anchors kidneys to surrounding structures
Parenchyma of kidney
Functional portion
Contains ~1 million nephrons (functional units)
Focusing on juxtamedullary nephrons
Kidneys: Renal corpuscle - components
Glomerulus (blood) - endothelium
- input: afferent arterioles
- output: efferent arterioles
Glomerular (Bowman’s) capsule - epithelium
- visceral: podocytes (modified epithelium)
- parietal: from outer wall of capsule (simple squamous)
Kidneys: Filtration membrane - parts
Fenestration (pore) of glomerular endothelial cell
Basal lamina of glomerulus
Slit membrane between pedicles
Differential filtering
Kidneys: Filtration membrane - fenestration
Prevents filtration of blood cells, but allows all components of blood plasma to pass
Kidneys: Filtration membrane - basal lamina
Prevents filtration of larger proteins
Kidneys: Filtration membrane - slit membrane
Prevents filtration of medium-sized proteins
Filtration unit and substrate
Filtration unit = nephrons
Substrate = blood supply
Kidney mass
~150g
Kidneys: Renal columns
Extension of cortex into medulla
Lots of blood vessels and tissue embedded here
Kidneys: Interlobar
Between 2 lobes
Kidneys: Nephrons - arrangement
Not randomly arranged
Very tightly packed in organised ways and all collect into a bunch (bouquet)
Kidneys: Calyces
Cup-like structures that collect urine from papillary
Start with smaller cups which merge to form bigger cups
Kidneys: Interlobar artery
Red blood vessel found between 2 lobes
Kidneys: Nephrons - classes
Some located higher up near cortical area
Others located lower down near medulla
Kidneys: Juxtamedullary nephrons
Nephrons close to cortical-medullary junction
Responsible for helping us make concentrated urine
Kidneys: Arcuate artery
Where renal artery arches as it comes up to the cortex at cortical-medullary junction
Gives rise to interlobular arteries
Kidneys: Interlobular arteries
Feed the lobules
Kidneys: Glomerulus / glomerular capillaries - form an important part of…
The filtration barrier
Afferent arteriole is ____ of the filtration apparatus
Upstream
Efferent arteriole - pathways
Can stay in cortex and feed cells that make up tubular parts of nephron
Or can delve deep into medulla and feed cells of tubular parts of nephron located here
Ascending vs descending vasa recta
Ascending: venous blood; relatively O2-poor blood
Descending: arterial blood; relatively O2-rich blood
Peritubular capillaries of medulla
Where gas exchange happens
O2 is absorbed by cells of nephron and CO2 is transported back into blood in peritubular capillaries
Kidneys: Where does blood transition from arterial to venous
In the peritubular capillaries
Peritubular capillaries: Venous blood - pathway
Travels into interlobular veins –> arcuate vein –> interlobar vein –> converge and exit kidney by renal vein –> IVC –> heart
Where does filtration begin
Renal corpuscles
Corpuscles
Capsulated structures
Interaction between what enables filtration to take place
Podocytes and underlying glomerular capillaries
Tgt they form the filtration barrier
Kidneys: Capsular / urinary space
Space between visceral and parietal epithelium
Where filtrate accumulates and eventually flows out the renal corpuscle into the tubular portion
Kidneys: What is the basal lamina made up of
BM secreted by podocyte
BM secreted by endothelial cells
Kidneys: Glomerular capillaries - texture
Not a smooth surface because has pores
Kidneys: Differential filtering - what happens to the proteins that get trapped
Either bounce back into blood circulation or are phagocytosed and recycled
Kidneys: Proximal convoluted tubule - cells
Have microvilli on apical membrane
Involved in transport
Kidneys: Distal convoluted tubule of many nephrons…
Combine and feed into a single collecting duct
Kidneys: Distal convoluted tubule - function
Monitors how things are going and provide feedback to influence the beginning of the process
Main functions of kidney
Regulation of water and electrolyte balance
Regulation of arterial pressure
Filters blood
Kidney - homeostasis
Blood pressure
Water and electrolyte balance
pH
Waste product removal
Kidney is part of ______ system
Circulation
Kidney: When things go wrong - symptoms
Swelling High blood pressure Shortness of breath Fatigue Nausea
Dialysis
Prevents build up of waste products
e.g. build up of high K+ –> heart rhythms go bizarre –> sudden death
Osmosis
The movement of water through a selectively permeable membrane
From an area of lower solute conc (high water conc) to higher solute conc (low water conc)
Osmotic pressure
The pressure required to prevent net water movement, i.e. pressure generated by the water moving inside a cell
Osmolarity
A measure of the osmotic pressure exerted by a solution across a semi-permeable membrane compared to pure water
Dependent on no of particles in solution (but independent of nature of particles)
Basically a measure of the conc of all the components in the solution
Osmolarity =
Molarity x dissociation factor
150mL NaCl + 1L water dissociates to give…
150 mM/L Na+ + 150 mM/L Cl-
= 300 mOsm/L
300mM urea + 1L water gives..
300 mOsm/L
Osmolarity usually refers to…
A container / beaker, not necessarily a cell
Hyperosmotic
A solution with a higher Osm than another
Isosmotic
2 solutions with the same Osm
Hyposmotic
A solution with lower Osm than another
Tonicity
Takes into account the conc of a solute and the ability of the particle to cross a semi-permeable membrane
i.e. ability of a solution to change shape of a cell
‘effective osmolarity’
NaCl - permeability
Low permeability
Urea - permeability
Higher permeability
Hypertonic
A solution with a higher POsm than another
Water will leave cell –> shrinkage
Isotonic
2 solutions with same POsm
Not net water movement
Hypotonic
A solution with a lower POsm than another
Water will move into cell –> swelling (and burst)
Disturbances in water balance: Dehydration
Loss of H2O from ECF
ECF osmotic pressure rises
Cells lose H2O to ECF –> cells shrink
Disturbances in water balance: Hydration
H2O enters ECF
ECF osmotic pressure falls
H2O moves into cell –> cells swell
Why maintaining osmolarity is important
Sets MP
Generates electrical activity in nerve and muscle
Provides energy for uptake of nutrients and expulsion of waste
Generation of intracellular signalling cascades
Fluid distribution in body - average 70kg male
60% fluid = 42L 2/3 intracellular = 28L 1/3 extracellular = 14L - 20% plasma = 2.8L - 80% interstitial = 11.2L
Major sources of water intake
Metabolism 8%
Foods 28%
Beverages 64%
Major sources of water output
Feces 4%
Lungs 12%
Skin 24%
Urine 60%
Electrolyte composition: High extracellular conc
Na+, Cl-, Ca2+ ions have high extracellular conc
Electrolyte composition: High intracellular conc
K+ ions have high intracellular conc
Electrolyte composition - similarities?
Amount in blood plasma and interstitial fluid are usually very similar
About ___L of fluid enters the renal tubules each day
180L
In the average adult, the entire extracellular fluid V is filtered about __ times a day
12
How much fluid that enters the renal tubules is reabsorbed
~178.6L reabsorbed
~1.4L urine produced each day
Excretion = ?
Filtration + secretion - reabsorption
Renal handling of water and solutes: Water
Filtration = total Reabsorption = most of total Excretion = small amount of total
Renal handling of water and solutes: Sodium
Filtration = total Reabsorption = most of total Excretion = small amount of total
Renal handling of water and solutes: Glucose
Filtration = total Reabsorption = total Excretion = 0
Renal handling of water and solutes: Creatinine
Filtration = total Reabsorption = 0 Excretion = total
What is reabsorption
The idea that you’re taking fluid out of your nephron and back into blood
Nephrons - pathway
Glomerulus Proximal tubule Loop of Henle: descending limb Loop of Henle: ascending limb Distal convoluted tubule Collecting duct
Glomerular filtration rate %
~25% of total renal plasma flow
180 L/day
Very constant, especially over a mean pressure of 80-140
Glomerulus has a similar solute conc to…
Plasma
Glomerulus lacks..
Proteins and other high molecular weight compounds
Free from blood cells
Glomerulus - coming in and going out
Have an arteriole coming in, a capillary bed, and an arteriole going out
The only place in body to have an arteriole before and after a capillary bed
Glomerulus: Capillaries - holes
Capillaries in capillary bed have big holes in them - easy for fluid to be filtered out
Glomerulus: Podocytes sit on top of _____
Capillaries
Blood flow to kidneys - regulation
Tightly regulated, thus glomerular filtration rate is relatively constant
Urine output is directly proportional to….
Renal/blood pressure
Kidneys - autoregulation
Good autoregulation
Pressure and blood flow through glomerulus is relatively constant
What is kidney autoregulation due to
Ability of arterioles to constrict - means flow through kidneys doesn’t change much
Particularly afferent arterioles
Glomerular blood hydrostatic pressure (GBHP)
The major force pushing fluid and solutes out the glomerular capillaries, i.e. BP inside glomerulus
Mechanical P between afferent and efferent arterioles
GBHP: Vasoconstriction of afferent vs efferent arterioles
Increases in arterial P can be buffered by vasoconstriction of afferent a
Decreases in P can be buffered by vasoconstriction of efferent a
GBHP: Pressure at afferent vs efferent arteriole
P at afferent arteriole slightly higher than at efferent arteriole
GBHP: Normal pressure inside glomerulus and arterioles
Glomerulus: 55 mmHg (halfway between afferent and efferent a)
Afferent: 60 mmHg
Efferent: 50 mmHg
GBHP: Afferent arteriole vasoconstriction - pressures
i.e. constricts before glomerulus
Glomerulus: decreases
Afferent: decreases
Efferent: same
GBHP: Efferent arteriole vasoconstriction - pressures
i.e. constricts after glomerulus
Glomerular: increases
Afferent: same
Efferent: increases
GBHP: What happens if BP drops
Efferent arteriole constricts –> increases P before constriction –> efferent P and glomerular BP increases
Glomerular filtration is dependent of…
Pressure gradients
NFP = ?
GBHP - CHP - BCOP
~10 mmHg
Net filtration pressure (NFP)
Determines how much water and small dissolved solutes leave the blood
Capsular hydrostatic pressure (CHP)
Pressure exerted on plasma filtrate by elastic recoil of glomerular capsule
~15 mmHg
Blood colloid osmotic pressure (BCOP)
The osmotic force which is the proteins left in the plasma - exert an increasing osmotic ‘pull’ on the water in plasma filtrate
~30 mmHg
GBHP vs CHP
GBHP = pressure inside capillaries CHP = pressure inside capsule (opposes)
Kidney stone affects which pressure
Fluid in kidney builds up –> increases CHP
Which pressure drives fluid back into capillaries
BCOP
Regulation of glomerular filtration - types
Autoregulation
Neural
Hormonal
Regulation of glomerular filtration: Autoregulation
Myogenic autoregulation or tubuloglomerular feedback
Blood vessels themselves respond to changes in pressure
Regulation of glomerular filtration: Neural
Increased sympathetic nerve activity –> (afferent) vasoconstriction –> reduces filtration
Regulation of glomerular filtration: Hormonal
Angiotensin II
Atrial natriuretic peptide
Longer term
Regulation of glomerular filtration: Hormonal - angiotensin II acts via…
Vasoconstriction of afferent and efferent arterioles
Regulation of glomerular filtration: Hormonal - atrial natriuretic peptide (ANP)
Responds to stretch of atria by relaxation of mesangial cells –> increases SA for filtration
Regulation of glomerular filtration: i.e. anything that…
- alters the GBHP (e.g. P in afferent artery)
- alters the SA available for filtration
Regulation of glomerular filtration: If you stretch a blood vessel…
It tends to constrict around it
Regulation of glomerular filtration: Which arterioles receive innervation from sympathetic nerves
Both afferent and efferent arterioles
Regulation of glomerular filtration: BP and sympathetic activity
High BP = high sympathetic activity
Natriuresis
The excretion of sodium
Diuresis
Getting rid of lots of water
Premature children and BP
Tend to develop high BP because SA available for filtration is reduced –> less glomeruli
Tubuloglomerular feedback - cycle
Increased GFR –>
Increased tubular flow rate (ascending limb) –>
Increased tubular Na+, Cl-, water content sensed by macula densa cells –>
Juxtaglomerular apparatus NO release decreased –>
Afferent arteriole vasoconstriction –>
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Macula densa
Sense amount of Na+ in ascending limb of nephron loop
Can give info to afferent arterioles - if lots of Na+, means there’s lots of fluid passing through tubules –> tells afferent arterioles constrict
Juxtamedullary vs cortical nephrons
Cortical: dilute urine, shorter
Juxtamedullary: important in production of concentrated urine (regulating Na+ and H2O balance), extends down into medulla
Where is interstitial fluid is very concentrated
Medulla
Where is there high conc of urea
Tip of nephron
Nephron structure and function
Cells in diff areas look diff and have diff functions
Where does the largest amount of solute and water reabsorption from filtered fluid occur
Proximal convoluted tubule
~60% glomerular filtrate
~60% NaCl and water
~100% glucose (except diabetes)
What area of the nephron is closest to the glomerulus
Proximal convoluted tubule
Do we urinate glucose
Generally no - all stored for later use
Exception is diabetes
Nephron: Proximal convoluted tubule - function
Highly active in membrane transport processes with reabsorption of water, ions and glucose
Nephron: Proximal convoluted tubule - structure
Highly developed brush border (microvilli) –> increases SA
Na+/K+ ATPase - location
Located on basal surface
Na+/K+ ATPase - function
Pumps Na+ into interstitial place
Maintains low Na+ in cell
Na+ movement into tubule cells
Occurs via symporters (e.g. Na+/glucose symporter) and antiporters (Na+/H+)
Nephron: Proximal convoluted tubule - glucose
Glucose and other solutes can diffuse down their conc gradient
Nephron: Proximal convoluted tubule - water
Na+ movement allows water movement via osmosis
Nephron: Proximal convoluted tubule - osmolarity
Similar to plasma
Na+/Glucose sympoter
Na+ moves in cell down its conc gradient and glucose moves with it
Nephron: Proximal convoluted tubule - diabetes
High levels of glucose –> saturate symporters –> urinate glucose
Nephron: Descending loop of Henle - permeability
Low permeability to ions and urea
Highly permeable to water
Nephron: Descending loop of Henle - water movement
Interstitial fluid is highly concentrated in medulla of kidney –> water moves out of tubule via osmosis –> urine becomes more concentrated
Nephron: Descending loop of Henle - bottom
By the bottom of the loop, the filtrate is v concentrated
~1200 mOsmol/L, whereas ECF ~300 mOsmol/L
Nephron: Thick ascending limb - permeability
Impermeable to water
Na+, K+ and Cl- actively reabsorbed
Nephron: Thick ascending limb (of Henle) - top
By the time the filtrate gets to top of loop, conc of ECF decreases –> gets rid of ions via Na/K/Cl symporter –> very dilute
~100 mOsmol/L
Nephron: Thick ascending limb - junctions
Very tight junctions –> water moves out
Loop of Henle: Countercurrent mechanism
Descending limb impermeable to NaCl
Ascending limb impermeable to water
Nephrons: Thick ascending loop provides…
Environment for thin ascending loop by pumping out ions
Nephrons: Loop of Henle is helped by…
Blood vessels
Nephrons: Descending loop of Henle is close to…
Descending side of capillary network
Nephrons: Thick ascending loop is close to…
Ascending side of loop of Henle
Nephrons: Does the ECF become diluted
Anything pumped out of the thick ascending loop is taken to thin descending loop and water coming out is taken away by veins –> doesn’t dilute the ECF
Loop of Henle vs vasa recta
Vasa recta moves in an opp direction to loop of Henle to take fluid away –> keeps a high concentration medulla
Nephron: Distal convoluted tubule and collecting duct - function
Additional reabsorption of NaCl
Nephron: Distal convoluted tubule and collecting duct - ADH
Water permeability is dependent on antidiuretic hormone
In absence of ADH, area is impermeable to water –> more reabsorption of Na+ and Cl- –> urine produced has little Na+ and Cl- –> urine dilute
Fluid dynamics: Water
Rapidly equilibrates throughout ICF and ECF
Decreases osmolarity
Fluid dynamics: Isotonic solution
Remain in ECF
No effect on plasma osmolarity
No gradient in isotonic solution for H2O to move into cell - not effective for dehydration
Antidiuretic hormone (ADH) - precursor
Made in hypothalamus and stored in vesicles in posterior pituitary
ADH release: Osmoreceptors
Innervate the hypothalamus, sense:
- increase in Na+ conc
- increase in osmolarity
Signal is sent to posterior pituitary and in response to APs, ADH is released into bloodstream
Where is ADH made
Nerve cells in hypothalamus
ADH: Osmoreceptors detect osmolarity in ____
ECF
Osmoreceptors - structure
Have ‘stretch-inhibited’ cation channels
Like a pyramid tethered with long arms - when cell shrinks, lots of stretch on arms –> opens stretch-activated channels
Osmoreceptors - channels
When cell shrinks due to hypertonic stimulus, cation channels open
Na+ enters cells and triggers APs
ADH AKA
Arginine vasopressin (AVP)
Plasma ADH and osmolarity
Plasma ADH increases as osmolarity increases
ADH release - blood volume
Increased blood volume = less ADH
ADH - threshold
Threshold for ADH release ~280 mOsm
Normally plasma osmolality is 290 mOsm
So, we usually have ADH circulating in our body with ability to increase or decrease
ADH - increased threshold results in…
Thirst (dehydration)
What hormone is most sensitive to osmolarity
ADH
What does ADH act on
The last part of the convoluted distal tubule and the collecting duct (i.e. end of nephron)
ADH - storage vesicles
ADH stimulates insertion of aquaporin-2 containing vesicles into the apical membrane
Aquaporin-2 is a water channel, so water can move from tubule into cell (water pore)
ADH - basolateral membrane
Always relatively permeable to water, so water can move via osmosis back into blood
ADH - steps
- ADH binds to membrane receptor
- Receptor activates cAMP second messenger system
- Cell inserts aquaporin-2 water pores into apical membrane via exocytosis
- Water is absorbed by osmosis into blood
ADH - ADH receptors
Detect and bind to ADH and sends a message into cell
ADH - apical vs basolateral membrane permeability
Normally apical membrane not permeable to water (but presence of water pores allows permeability)
Basolateral permeable to water
ADH - urine
ADH facilitates reabsorption of water in distal tubule and collecting duct –> concentrated urine
Collecting ducts move through the ____ of the kidney
Medulla
As we move down the collecting duct, there’s a gradient for water to…
Move out of it, so water pores allow them to easily move out to dilute the medulla
End of collecting duct - osmolarity
Can get up to 1200 mOsm
ADH release - types of baroreceptors
Both arteriole and cardiopulmonary baroreceptors
ADH release - baroreceptors, blood P and blood V
Decreased baroreceptor activity, decreased blood V or P = ADH release
Overall, what factors affect ADH release
Anything that causes an increase in osmolarity, an increase in conc, or a decrease in blood V
Renin-Angiotensin-Aldosterone (RAA) system - functions
Maintaining Na+ balance
BP regulation
ADH: Dehydration
Increase in osmolarity and change in blood V = ADH increases
ADH: Drinking too much water
ADH decreases
Juxtaglomerular apparatus
Where distal tubule borders the glomerulus
Juxtaglomerular apparatus: Macula densa cells
Respond to a decrease in NaCl content by increasing prostaglandins
Baseline regulation to keep it even - not involved in blood P regulation, just prevents damage of kidneys
Juxtaglomerular apparatus: Juxtaglomerular (granular) cells
In afferent arteriole
Release renin
Juxtaglomerular apparatus: Pressure
Decrease in pressure in afferent arteriole acts on juxtaglomerular cells –> release renin
Juxtaglomerular apparatus: Macula densa cells - fast or slow
Buffers quick changes
Juxtaglomerular apparatus: Renin release - fast or slow
Slow - long-term effect that respond to more subtle changes
Renin is released primarily due to…
Low Na+ in nephron
Hormones - speed
Usually take a while
Triggers for renin release from juxtaglomerular (granular cells
Low NaCl conc in distal tubule (Na+ depletion)
Decreased perfusion pressure (by granular cells, afferent arteriole)
Increased sympathetic activity (e.g. via baroreflect)
i.e. low BP, low BV, low Na+
Renin release: Macular densa cells are sensing…
Low Na+
Renin-Angiotensin System: Active hormone
Angiotensin II
Others (angiotensinogen and angiotensin I) are precursors
Renin is a(n) _______
Enzyme
Renin-Angiotensin System: Rate limiting step
Renin is the rate limiting step of the production of angiotensin II
Renin-Angiotensin System: ACE
Usually lots present
Usually the target when wanting to reduce angiotensin II because less side effects
Aldosterone - release
From adrenal cortex in response to angiotensin II
Aldosterone - what does it act on
Distal tubule and collecting ducts to increase transcription of Na/K ATPase pumps –> increases Na+ reabsorption and K+ excretion
Aldosterone - water
Water reabsorption may also increase via osmosis if ADH is present
Aldosterone - main functions
Na+ and water retention
Angiotensin II - high levels
Quite a potent vasoconstriction in kidney and smooth muscle
Can stimulate thirst
RAA system summary - dehydration
Na+ deficiency and haemorrhage –> decrease blood V –> increase renin –> increase angiotensin II –> vasoconstriction of arterioles –> increase BP until norm
OR:
increase aldosterone –> increase Na+ (and water) reabsorption in –> increase blood V -> BP increase until norm
Angiotensin II and salt
Increased salt –> reduced angiotensin II –> reduced renin because of change in arteriole P
Chips (increased salt) - effects
Increased intake of NaCl in ECF –> water moves out of cell –> increased blood V and osmolarity (?)
ADH and chips
Increase in blood V is major trigger so ADH doesn’t help much
Salt vs water balance
ADH: important in maintaining water balance
RAA system: important in maintaining salt balance
2 systems allow for independent control of water and salt levels in body
Haemorrhage - fluid loss is…
Isosmotic
Lose both water and salt so need both RAA system and ADH
Blood loss is…
Hypovolemic / isotonic
What is blood loss sensed by
Juxtoglomerular cells and arterial baroreceptors
Blood loss leads to increased…
Sympathetic activity
ADH
Renin / angiotensin II / aldosterone
–> vasoconstriction and conservation of water and Na+
Atrial natriuretic peptide (ANP) - acts to..
Reduce renin, ADH and aldosterone release
Increase GFR
Reduces Na+ and water reabsorption
Timescale:
Baroreceptors = second
Osmolarity = ~1-2 min
ADH at least half an hour, 3 hours before any change in blood levels
Aldosterone ~4 hours
Where are glomerular capillary endothelial cells found
In renal corpuscle
Gradient for transport of many substances is produced by…
The Na/K ATPase pump
Perfusion P and blood flow
Decreased perfusion P –> decreased NV –> decreased renal blood flow
Renin and GFR
Decreased GFR = increased renin
Selective vasoconstriction of the efferent arteriole leads to….
Increased P in glomerular capillary network
Dehydration - aquaporins
Dehydration –> more aquaporins inserted into membrane collecting ducts
The countercurrent exchange in the vasa recta maintains..
High conc of NaCl in ECF