Renal System Flashcards
What are the 7 main roles of the kidneys?
excretion of metabolic products and foreign substances
retrieval and retention of useful substances
regulation of body fluid osmolarity and volume
regulation of electrolyte balance
regulation of acid-base balance
production and secretion of hormones
the storage and voiding of urine
Why is maintenance of plasma fluid volume important?
maintains the equilibrium of other fluid areas in the body
what are the main sections of the urinary tract?
kidney, ureter, bladder and urethra
what section of the nervous system innervates the kidneys?
sympathetic branch of ANS
What sections is the medullary layer of the kidney split into?
renal pyramids and papillae
what does the renal papillae drain into?
minor and major calyxes and then the pelvis of the kidney
What is the basic functional unit of the kidney?
nephron
what are the two types of nephron?
cortical nephrons and juxtamedullary nephrons
where are cortical nephrons found?
in the cortex
where are juxtamedullary nephrons found?
deep into medulla
What is the role of juxtamedullary nephrons?
urine concentration due to their long loops of Henle
what is the main role of cortical nephrons?
absorption and secretion
where is fluid filtered from into the nephron?
the blood stream
what is ultrafiltrate similar to?
plasma
how does ultrafiltrate differ from plasma?
doesn’t contain proteins but is otherwise the same
what happens to most of the filtrate?
it is reabsorbed after modification
what happens to the excess ultrafiltrate that is not reabsorbed?
voided as urine
what type of capillaries are found in the glomerulus?
fenestrated
what can fit through fenestrated capillaries?
plasma proteins, water, nutrients, waste and electrolytes
what is the glomerulus?
the capillary network in the kidneys where ultrafiltration occurs
what will not fit through fenestrated capillaries?
formed elements of blood (e.g. RBC)
where is the only place in the body where capillary bed is fed and drained by arterioles?
glomerulus in kidneys
what is the Bowman’s capsule?
contains glomerulus
what occurs within the Bowman’s capsule?
filtration to create ultrafiltrate
Describe the path from Bowman’s capsule to collecting duct
proximal convoluted tubule - loop of Henle - distal convoluted tubule - collecting duct
what happens in the proximal tubule?
most of the fluid is reabsorbed along with vital nutrients
what happens in the loop of Henle?
urine concentration is controlled
what happens in the distal convoluted tubule?
fine tuning of electrolyte concentrations
What does the blood supply of the kidney consist of?
two capillary beds in series (one after the other)
what are the glomerular capillaries the site of?
filtration
is blood leaving the glomerulus oxygenated?
yes
what is the name of the vessels that supply and leave the glomerulus?
afferent and efferent arterioles
what is the name of the second capillary bed in the kidney?
vasa recta
what does the vasa recta surround?
the nephron
what happens at the vasa recta?
site of gaseous exchange and collection of solutes and water reabsorbed by nephron
how is the juxtaglomerular apparatus (JGA) formed?
the distal convoluted tubule loops back and makes physical contact with the glomerulus which forms the JGA
what is the importance of the JGA?
secretes important hormones
what remains the same in the kidney despite changes in the arterial blood pressure?
glomerular filtration rate
what does autoregulation of renal blood flow mean?
blood flow remains constant despite changes in arterial blood pressure
between what pressures is renal blood flow autoregulated?
60 to 160 mmHg
if renal blood flow is autoregulated what does this mean for glomerular filtration rate
will also be relatively constant despite changes in arterial blood pressure
what is a proposed explanation for autoregulation?
if blood pressure increases the initial increased flow will stretch the muscle in the arteriole wall and cause it to contract. If GFR were to increase this is sensed by cells in the JGA which release a constrictor
why must RBF and so GFR remain so constant?
kidney requires a constant supply of glomerular filtrate
what is the endothelium of the glomerulus formed of?
3 layers including a basement membrane
what is the function of podocytes?
envelop the fenestrated capillary and prevent large molecules from leaving the capillary (e.g. albumin). Are a barrier to leakage of protein into ultrafiltrate
what are the two processes found on popcytes?
primary and secondary
what is the gap between secondary processes of podocytes called?
filtration slit
what forms the major filtration barrier to macro molecules?
the podocyte
what do the capillary fenestrations allow?
movement of water, smaller molecules and ions
why does fluid cross the glomerular capillaries into the nephron?
due to physical forces across the capillary wall
what are the forces which act on fluid to move it from glomerular capillaries to the nephron?
hydrostatic pressure in the capillary from blood pressure
what are the forces which act on fluid to move it from nephron to the glomerular capillaries?
osmotic forces across the capillary due to plasma proteins
how is the net hydrostatic force calculated
hydrostatic pressure of capillary - hydrostatic pressure in Bowman’s capsule
how is the net reabsorption force calculated?
osmotic (oncotic) pressure of capillaries - osmotic (oncotic) pressure of Bowman’s capsule
in a healthy person what will the net filtration force create?
net force out of the capillary
what is the result of glomerular filtration forces?
a large volume of filtrate per unit time which is cell and protein free
the concentration of small solutes is the same as in plasma
what is creatinine a product of?
waste product of natural muscle breakdown
why is the amount of creatinine in urine due to glomerular filtration only?
it is freely filtered, not reabsorbed from tubule, not secreted into tubule and inert
what is a common blood borne biomarker of GFR?
creatinine
how can creatinine indicate kidney issues?
amount will decline if GFR declines which indicates state of kidney. There is an expected amount in urine in a healthy person
what is urinary excretion of creatinine proportional to?
it’s delivery by the renal artery
what is the proportionality of urinary excretion of creatinine and it’s delivery by the renal artery called?
creatinine clearence
how can creatinine clearance be calculated?
clearance = urine production rate/plasma creatinine concentration
what is the estimate of rate of filtration an important measurement of?
the ability of the kidneys to function properly
what is the preferred reference for the blood flow in the kidneys?
renal plasma flow
what is renal plasma flow usually?
750 ml/min
how much of the renal plasma flow is used as glomerular filtrate?
15-20%
how much urine is usually produced per minute?
1 ml
what percentage of filtrate is reabsorbed along the nephron?
99%
if renal plasma flow isn’t used as glomerular filtrate what happens to it?
leaves the glomerulus through the efferent arteriole
how much of total tubular reabsorption does proximal tubule reabsorption make up?
70%
what happens in the proximal tubule?
reabsorption of several vital solutes as wel as the bulk of the filtered fluid. It is the site of secretion from the blood to tubular fluid
what state does fluid in the proximal tubule remain in throughout passage through the tubule?
isotonic (isosmotic)
what is the average glomerular filtration rate in a healthy young adult?
120 ml/min or 175 ltres per day
what happens to glomerular filtrate/
reabsorbed either in the proximal tubule, loop of Henle or collecting duct. alternatively it is voided as urine
what are the two surface of the proximal tubule cells?
apical surface facing the tubular lumen and baso-lateral surface on the inner layer close to the blood vessels
what are the two main features of the apical cell surface of the epithelial cells?
microvilli and many mitochondria
what is the function of the microvilli on the apical surface of epithelial cells?
greatly increases surface area which enhances transport capacity
what is the significance of many mitochondria in the epithelial cells?
shows lots of metabolic activity
what are the 4 vital functions of the proximal tubule?
reabsorption of the bulk of filtered NaCl and isotonic NaCl
reabsorption of essential solutes
contribution ot the regulation of body fluid pH
secretion of some orgainic molecules
where does secondary active transport occur in the epithelial cell of the proximal tubule?
apical side of the epithelium
what is the movement of Na+ indirectly coupled to when it moves with it’s concentration gradient across the apical layer?
ATP hydrolysis to maintain the Na+ gradient across the cell membrane
what does the position o fth secondary and primary active transporters do to transport?
gives directionality
what is the primary active transport pump on the baso lateral layer?
Na+/K+ ATPase
what is happening when substances move from apical to basolateral layers?
reabsorption
what is happening when substances move from basolateral to apical layers?
secretion
what is Na+ transport across the apical membrane enabled by?
cotransport with another essential solute (e.g. glucose)
what will happen to the solute that is co transported alongside Na+?
it will diffuse out across the basolateral membrane
How is the membrane potential created in the proximal tubule?
by the transport of Na+ ions out of the tubule by secondary active transport
what is the effect of the membrane potential in the proximal tubule created by transport of Na+ ions?
anions can now flow into blood vessels down concentration gradient
what must the number of Na+/glucose transporters ensure?
all glucose is reabsorbed under normal circumstances
what are some other Na+ coupled transporters?
those for bases, neutral or amino acids
what ions flow down their electrochemical gradient out of the proximal tubule?
Cl-
how is isotonic NaCl transported?
Cl- following on electrochemical gradient created by co transport of Na+
how is there no concentration of tubular fluid?
movement of water by osmosis and NaCl by transport and creation of electrochemical gradient
what is glucose reabsorption mediated by?
carriers
what is a consequence of carrier mediated glucose reabsorption?
it has a maximum transport rate
what is the maximum transport rate of glucose known as?
tubular transport maximum or Tmax
at what concentration can the kidney completely reabsorb the filtered glucose load?
normal plasma (and filtrate) concentrations (4-6mM)
where may blood glucose levels rise to shortly after eating?
8mM
is the short term rise of glucose after eating enough to exceed Tmax?
no
what is Na+ across the membrane also enabled by?
counter transport with H+ ions
how is Na+ transported across the basolateral membrane after counter transport with H+ across the apical membrane?
primary active transport with sodium/potassium ATPase
how does the cell regulate intracellular pH?
extruding excess H+
what is H+ produced in the cell by?
metabolism exchange for Na+
how does Cl- and water move when Na+ is counter transported with H+?
Cl- moves along electrochemical gradient and water by osmosis
what element of body fluids does the kidney play a vital role in maintaining?
the correct pH
what is the normal pH of plasma?
7.35-7.45
what is the intracellular pH of most cells?
7.0-7.1
what is the activity of most enzymes dependent on?
pH
under what circumstances is the activity of pH dependent enzymes be greatest?
at their optimum pH
where can an excess of CO2 come from in the tubular fluid?
the blood
can Co2 enter the cell easily?
yes
what does CO2 react with H2O to form?
H+ and HCO3-
what is the creation of H+ and HCO3- from CO2 and H2O catalysed by?
carbonic anhydrase
where does HCO3- leave the cell?
across the basolateral membrane by a number of co and counter transporters
where does H+ leave the cell?
across the apical membrane via Na+/H+ counter transporter
what happens to some of the H+ in the tubule?
bound by buffers and excreted in urine
what happens to other H+ molecules which are not bound to buffers and lost in urine?
react with HCO3- catalysed by carbonic anhydrase to restart the cycle
what is a key feature of proximal tubule secretion?
able to rid the body of certain substances
what is the proximal tubule able to excrete?
a number of organic ions and cations
what are the organic ions and cations secreted by the proximal tubule the products of?
end products of metabolism
what effect can proximal tubule secretion have on therapeutic drugs?
may limit the time that they are in circulation and so reduce their efficacy
what proportion of resting cardiac output do the kidneys receive?
25%
define osmolality
concentration of impermeable solutes per kg of solute
what happens if a cell is placed in a hypotonic solution?
water moves into the cell and it swells
what happens if a cell is placed in a hypertonic solution?
water leaves the cell and it shrinks
what is the kidneys’ response to dehydration?
to retain water and produce a small volume of concentrated urine
what is the risk of overhydration?
dilatation of plasma
how do the kidneys respond to overhydration?
produce a large volume of dilute urine
why is plasma osmolality regulated?
to prevent cell swelling or shrinkage
how is plasma osmolality regulated?
by controlling water influx and efflux from the body
what methods of intake and output of water from the body are physiologically controlled?
intake of water through drinking and output via urine production
why is the control of drinking and urination so importnat?
their values are similar
what is an important mode of control in regulation of plasma osmolality?
generation of urine of different concentrations
under what circumstances is urine concentrated?
if the body must conserve water to replace excessive loss
when is urine dilute?
if the body needs to lose excessive water
what is normal plasma osmolality?
290 mosmol.kg-1 H2O
how much variation in plasma osmolality will activate compensation mechanisms?
1% - tightly controlled
what is a change in plasma osmolality detected by?
osmoreceptors in the hypothalamus
when a change is detected by the osmoreceptors in the hypothalamus what is initiated?
release of ADH from the pituitary gland
a change in the perception of thirst from the thirst centre
what is the effect of ADH?
influences urine concentration
what is the effect of the thirst response?
water intake is altered
what sort of feedback process is plasma osmolality regulation?
negative feedback process
what is ADH?
Anti-diuretic hormone
what type of hormone is ADH?
peptide
where is ADH secreted from?
the posterior pituitary gland
what are the 3 actions of ADH on the kidney?
it increases water permeability of the collecting duct
increases NaCl reabsorption in the thick ascending limb
increases urea permeability in the inner medullary region of the collecting duct
what is the net effect of ADH?
to aid reabsorption by the kidney
what neurones is ADH produced in?
supraoptic and paraventricular
Where is ADH transported to once it is produced?
axon terminals in the posterior pituitary
what causes ADH to be released into the blood?
a rise of plasma osmolality a small as 1% which activates hypothalamic neurons
when is ADH release reduced?
when osmolality falls
what does the plasma concentration of ADH between 0.5 and 5 pg.ml-1 account for?
100-1250mosmol.kg H2O-1 urine osmolality
what effect does an increase in ADH have on urine output?
a small volume of concentrated urine
what effect does a decrease in ADH have on urine output?
a large volume of dilute urine
in what osmotic state is the tubular and interstitial fluid when it leaves the proximal tubule?
isosmotic
where is sodium chloride and potassium chloride absorbed from in the nephron?
ascending limb of the loop of Henle
what portion of the nephron is impermeable to water?
ascending limb of the loop of Henle
which part of the loop of Henle is permeable to water?
the descending loop of Henle
due to the properties of the ascending and descending loops of Henle what happens to the fluid within it?
becomes hyper osmotic
what is the net result of the counter current mechanism in the loop of Henle?
an osmolality gradient is generated in the medullary interstitium
where is there hypo-osmotic fluid in the nephron?
in the distal tubule and collecting duct
how is the concentrating mechanism set up?
by ion transport in the ascending limb of the loop of Henle which is impermeable to water
what pump is used in transport of ions to create concentrated urine ?
Na+/K+/2Cl- co-transporter and a baso-lateral Na-pump
how much of the filtered Na+, K+ and Cl- is reabsorbed?
about 20%
what can the Na+/K+/2Cl- co-transporter be blocked by?
loop diuretics
summerise the the counter-current mechanism
an osmolarity gradient is generated in the medullary interstitium.
fluid entering the distal tubule and collecting duct is hypo-osmotic
how does ADH increase the water permeability of the distal tubule and collecting duct cells?
binds to the membrane of the distal tubule and collecting duct
why does water leave the hypotonic nephron fluid?
equilibrate with with hypertonic medullary interstitium fluid
tubular fluid becoming more concentrated leads to?
concentrated urine
what is the name of the receptor ADH binds to on the basolateral surface of the tubule cell?
a V2 receptor
what does the binding of ADH to V2 receptors on the basolateral surface of the tubule cell do?
stimulates adenylate cyclase to generate cAMP and activate protein kinases
what does the generation of cAMP and activation of protein kinases do?
increases the insertion of water channels into the apical surface of the cell and so increase water permeability
what is the name of water channels in the basolateral surface?
aquaporins
what does the increase in aquaporins in the descending loop of Henle lead to?
water flowing from the more dilute tubular fluid to the hyperosmotic medullary interstitium which concentrates the tubular fluid
describe the thirst mechanism
increased ECF (plasma) osmolarity is associated with reduced saliva and dry mouth. This increases activity of osmoreceptors in hypothalamus leading to stimulation of hypothalamic thirst centre. This increases the sensation of thirst so the person needs to drink. Water moistens the mouth and throat and stretches stomach and intestine. Water is then absorbed from the GI tract returning plasma osmolarity to normal.
what is control of blood volume also sometimes referred to as?
control of effective circulating volume
what do the kidneys control?
plasma constituents
why does plasma volume affect blood volume?
the cellular component of blood is usually fixed so and volume changes will be caused by changes in plasma
as all fluid compartments of the body are linked, how does this affect volume control?
if volume of one is altered it will affect the volume of the others
how does the kidney indirectly control plasma volume?
by regulating Na+ excretion
what is blood pressure determined by?
the rate of blood returning to the heart and therefore the preload on the ventricles
if blood volume is controlled what else may be controlled?
arterial blood pressure
what does decreased venous return lead to according to Starlings Law?
reduced preload and so reduced SV
how might the kidneys respond to hypovolaemia?
sensing reduced blood pressure and flow, reducing Na+ loss in the urine and so reducing water loss in the urine
how can blood volume be restored?
increase Na+ retention which will cause water to be drawn into the blood by osmosis, this increases blood volume
what do the kidneys regulate in order to maintain blood volume?
sodium loss into urine
where are the high pressure sensors of blood volume found?
systemic arterial
where are the low pressure sensors of blood volume found?
systemic venous and pulmonary
what do high pressure sensors respond to?
variations in arterial blood pressure
where are arterial barorecptors located?
carotid sinus and aortic arch
how do the arterial baroreceptors respond to hypovolaemia?
increases sympathetic activity to the kidneys due to a fall in pressure and reduced baroreceptor signalling
what does the juxtaglomerular apparatus of the kidney respond to?
reduced blood pressure
how does the juxtaglomerular apparatus respond to hypovolaemia?
hormonal response leads to reduced Na+ loss and so reduced water loss in response to reduced blood pressure/renal flow
what are low pressure sensors used for?
excretion of retained plasma fluid
where are the low pressure sensors found within systemic venous and pulmonary areas?
cardiac atria and pulmonary vasculature
during hypovolaemia what do sympathetic nerves innervate?
afferent arterioles
why is sympathetic activity increased during hypovolaemia?
part of the baroreceptor reflex
describe the baroreceptor response to reduced blood pressure
baroreceptor signalling reduces leading to increased sympathetic activity and constriction of afferent arterioles. This leads to reduced glomerular filtration and reduced filtered load of Na+ which in turn reduces water loss. Blood volume is restored
what is the juxtaglomerular apparatus involved with?
replacement of lost volume
what is the juxtaglomerular apparatus?
structure in the nephron where the distal tubule makes close contact with the glomerulus and it’s vasculature
what do juxtaglomerular cells secrete in response to low blood flow or increased sympathetic activity?
the hormone renin
what is the effect of renin?
directly involved with Na+ and so water reabsorption at the distal tubule
describe the response of juxtaglomerular apparatus to reduced blood pressure
reduced blood flow/pressure triggers renin secretion from the kidney this reduces Na+ secretion and so water loss so blood volume is restored
what is the renin-angiotensin-aldosterone system (RAAS) key in?
regulation of blood volume by controlling NaCl and so water reabsorption by nephron
what type of enzyme is renin?
proteolytic enzyme
what is the substrate of renin?
circulating angiotensinogen
what is angiotensinogen produced by?
the liver
when is angiotensinogen is hydrolysed by renin what is the product?
decapeptide known as angiotensin I
what is angiotensin 1 converted into?
octapeptide angiotensin 2
what is angiotensin 1 converted into angiotensin 2 by?
an angiotensin converting enzyme (ACE) in the lung
what are the 3 roles of angiotensin 2?
exerts vasoconstrictor response
stimulates ADH release and so water retention by kidney
stimulates aldosterone release from adrenal cortex and so increases Na+ retention by kidney (and thereofre reduces water loss)
what type of hormone is aldosterone?
steroid
where is aldosterone secreted from?
zona glomerulosa of the adrenal glands
what is aldosterone secreted by?
angiotensin 2 stimulating its release from adrenal cortex
what does circulating aldosterone bind to?
it binds to a receptor on the nephron basolateral membrane
what does the receptor - aldosterone complex stimulate?
transcription (nucleus) of apical membrane Na+ channels (ENaC)
what effect does the increased number of ENaC channels on the apical membrane of the nephron have?
increases NaCl reabsorption via principal cells in the distal tubule/collecting duct
what substances will follow Na+ across the apical membrane when it is moved through ENaC channels and into the blood stream?
Cl and water
Summarise the RAAS control of plasma volume
reduced blood volume/pressure
reduced renal blood flow
increased renin secretion
increased angiotensin 2
increased aldosterone secretion from adrenal glands
increased sodium, and so water, reabsorption by kidneys
what will an increase in blood volume or venous return cause in the atria?
excessive stretch of atria and release of ANP
where is ANP stored?
atrial myocytes
what does ANP stand for?
atrial natiuretic peptide
what does ANP cause?
natriurisis
what is natriurisis?
excretion of Na+ (as NaCl) and so water
what are the 5 effects of ANP release?
inhibition of aldosterone secretion
inhibition of renin secretion
vasodilation of afferent arteriole leading to increased glomerular filtration rate
reduced Na+ absorption in convoluted tubules
inhibition of ADH release leading to increased water excretion
what ions does the kidney regulate?
K+ and Ca+
where is the bulk of body K+ found?
in the intracellular space
how does regulation of K+ occur?
by keeping the extracellular concentration of K+ within very narrow margins
what is the normal value of K+ within the body?
3.5 to 5.5 mmol/l
what is hyperkalaemia?
increase of K+ to greater than 5.5 mmol/l
what does hyperkalaemia cause?
membrane depolarisation of excitable cells and increases excitability
what is hypokalaemia?
a decrease of K+ to less than 3.5 mmol/l
what does hypokalaemia cause?
hyperpolorization of cells and decrease in excitability
what happens to an excitable cell during hyperkalaemia?
cell potential is closer to threshold meaning it is easier to excite/propagate action potential
what is a key danger during hyperkalaemia?
cardiac electrophysiological problems such as arrhythmias due to the cell being more excitable
what happens to an excitable cell during hypokalaemia?
the cell is much harder to excite and so normal AP will not be propagated as quickly as normal
what are the symptoms of hyperkalaemia?
non-specific - palputations, muscle weakness and breathlessness
what are the characteristic ECG changes shown in a hyperkalaemic patient?
tall T waves, prolonged QRS complex in severe cases
what are the symptoms of hypokalaemia?
arrhythmia, fatigue, muscle damage and constipation
where is 90% of the filtered load of K+ reabsorbed in the kidneys?
proximal tubule
where does most of the K+ secretion into urine take place?
the distal tubule
what are the 2 main regulators of K+ secretion?
plasma K+ and plasma aldosterone
what does an increase in plasma K+ cause?
enhances secretion of aldosterone and depolarizes cells of the zona glomerulosa in the adrenal cortex
what does an increase in plasma aldosterone cause?
enhances secretion of potassium through activation of apical K+ channels
what stimulates the release of aldosterone from the adrenal cortex?
Ca2+ influx into the cell
how does hyperkalaemia increase K+ secretion?
stimulates the adrenal cortex to release aldosterone
what does aldosterone do to increase K+ secretion?
increase sodium/potassium ATPase sites at the basolateral membrane and so stimulate their activity
increase presence of Na+ and K+ channels at the apical membrane
What effect does hypokalaemia have on aldosterone?
opposite to hyperkalaemia
where is the bulk of body Ca stored?
in the bones and teeth
how much of total Ca in the body is exchangeable with ECF?
1%
what are the short term effects of hypocalcaemia?
increase the excitability of nerves and muscles
what are the long term effects of hypocalcaemia?
demineralisation of bones
what are the different states of Ca?
bound and ionised
what is the normal value of Ca2+ in plasma?
2.2-2.6 mmol/l
what does Ca2+ tend to bind to in the blood?
plasma proteins (e.g. albumin and anions such as HCO3)
How much does the ionised form of Ca2+ make up of the whole?
50% of the total
what are Ca2+ sites competitively bound by?
H+
as Ca2+ sites are competitively bound by H+ what does alkalaemia cause?
more Ca2+ can be bound and the ionised fraction is reduced
what is alkalaemia?
increased plasma pH
what is the precursor of activated vitamin D?
cholecalciferol
what is cholecalciferol obtained from?
the diet and action of UV light on the skin
is cholecalciferol active?
no - functionally inactive and must be converted to active form
what is the active form of cholecalciferol (vitamin D)?
1,25 (OH) vitamin D3
what happens to cholecalciferol in the liver?
hydroxylation to 25 (OH) vitamin D3
what happens to 25 (OH) vitamin D3 in the kidneys?
hydroxylated to 1,25 (OH) vitamin D3
what can 25 (OH) vitamin D3 also be hydroxylised to in the kidney?
24,25 (OH) vitamin D3
what is the purpose of 24,25 (OH) vitamin D3?
means to prevent the excessive generation of 1,25 (OH) vitamin D3
what causes hypoxia of a tissue?
too little O2 delivered
what are the 3 factors which determine the amount of CO2 delivered to tissues?
% saturation of haemoglobin with O2
the amount of haemoglobin in any volume of blood (e.g haematocrit or individual cells)
the flow of blood (CO)
what is the effect of reduced RBC number?
reduced O2 delivery to tissues and the tissue becomes hypoxic
what is blood cell development called?
erythropoiesis
what is erythropoietin?
hormone which is synthesised by the kidneys that activates production of RBC
what does tissue hypoxia produce?
hypoxia inducible factor-2 alpha (HIF-2a)
what organs is hypoxia inducible factor-2 alpha produced by?
in foetuses and neonates - liver
in adults - kidneys
what does hypoxia inducible factor-2 alpha stimulate?
interstitial fibroblast-like cells to release erythropoietin
what does erythropoietin do one released from near the kidney tubules?
goes to bone marrow to encourage production of erythrocytes. Erythropoiesis restores O2 delivery to tissues
what is the role of the urinary tract?
carries urine from the kidneys to be stored in the bladder and then voided
what happens in the upper urinary tract?
urine is collected in the renal pelvises and conveyed by the ureters to the bladder
why can’t urine empty from the bladder during storage?
because the urethra (outflow tract) presents a high resistance to fluid flow
what must happen to allow urine to be voided?
bladder contracts and outflow tract relaxes
where does the wave of peristalsis in the ureter originate?
pacemaker cells in the renal pelvis
what smooth muscle is the bladder lined by?
detrusor
what sort of muscle is the urethra formed from?
smooth muscle
what is the external urethral sphincter formed of?
a ring of skeletal muscle which surrounds the urethra
what is the detrusor muscle supplied by?
post-ganglionic parasympathetic nerve fibres which release acetylcholine to contract the muscle
what is the innermost layer of the bladder formed of?
urothelium
what is a key function of urothelium?
provides a protective layer by forming a tight barrier to prevent urine leaking to the underlying tissues
what does urothelium release when stretched?
agents which excite afferent nerves
describe what happens during bladder filling without leakage
volume increase by up to 500ml with little rise in pressure due to bladder compliance, there is no leakage due to the contracted state of the urethra and external urethral sphincter. The subject senses bladder filling due to sensory nerve signalling but he brain suppresses voiding
where do afferent nerves from the bladder synapse within the brain?
peri-aqueductal grey (PAG) neurons in the midbrain
where are the signals from the afferent nerves of the bladder sent once they reach the peri-aqueductal grey (PAG) neurons in the midbrain?
sent to anterior cingulate gyrus insula and pre frontal cortex via the thalamus
what does the process of transmission of afferent bladder signals do to the type of signal?
changes it to sensation of bladder filling
where is the decision not to void the bladder made?
medial pre-frontal cortex
how is storage of urine maintained?
by chronic inhibition of the PAG and so the mictruition centre
what 3 nerves are involved in urine storage?
pelvic nerve, pudendal nerve and hypogastric nerve
which nerve activity is suppressed in order to store urine?
the parasympathetic (pelvic) nerve so the bladder is relaxed
what nerves are activated to ensure bladder storage?
sympathetic (hypogastric) and somatic (pudendal) cause urethra and external sphincter to contract
how does the brainstem cause the bladder to store urine?
suppresses pelvic nerve and so bladder relaxes
activates pudendal nerve and hypogastric nerve to cause external sphincter and urethra to contract
describe what happens during voiding of the bladder
brain makes the decision to void (is is socially acceptable). The bladder wall contracts and pressure in the urethra lumen increases soon after the flow starts due to rising pressure and relaxation of outflow tract muscles. The sensation of bladder fullness is reduced and the bladder completely empties
how is the decision to void made in the brain?
once afferent input is sufficient the decision to void is made
what happens within the brain once the decision to void urine is made?
the medial pre-frontal cortex relaxis it’s inhibition of PAG. The hypothalamus also provides a signal
what is the effect of ending inhibition of the PAG when the decision to void urine is made?
PAG excites PMC to send descending motor output to the sacral spinal cord to relax the urethral sphincter and contract the detrusor so that voiding occurs
how does the brainstem cause voiding of the bladder?
pelvic nerve is activated causing contraction of bladder. Pudendal nerve and hypogastric nerve is suppressed to cause relaxation of external sphincter and urethra
