Flashcards in FUNCTIONS OF THE KIDNEY Deck (102):


-Removing metabolic waste from the extracellular fluid
(urea, acids)
-Controlling the volume of extracellular fluid (close link
to blood pressure)
-Maintaining optimal concentrations of vital solutes in
the extracellular fluid (Na, K, H, Ca, Mg, Cl, Phos)


How much of the cardiac output goes to the kidneys



three basic processes of the nephron

glomerular filtration - filtering of blood into tubule forming the primitive urine (glomerular filtrate)

tubular reabsorption - selective absorption of substances from tubule to blood

tubular secretion - secretion of substances from blood to tubular fluid


what is the glomerular filtration barrier

A unique structure allowing extracellular fluid to be
filtered and to leave the body:
– Specialised capillary endothelium
– Glomerular basement membrane – collagen based
– Podocyte foot processes


Normal GFR approx

100ml/min = 144L per day


movement of solutes and water across membranes ..


specific membrane channels
- energy dependent
- down a conc gradient
- down an electrical gradient
-down an osmotic gradient

controlled by systemic and local mediators


PCT cell features

basolateral membranes with infoldings for ATPase
apical membrane with microvillae and aquaporins .


how much sodium chloride is reabsorbed in PCT

approx 70%
nearly all amino acids and glucose is reabsorbed in PCT


what are the loop of henle rules

1. Thick ascending limb is
impermeable to water, but actively
transports sodium, potassium and
2. Thick ascending limb provides the
concentration gradient to promote
water reabsorption from the thin
3. Thin descending limb is freely
permeable to salt and water
4. Vasa recta doesn’t wash away the
gradient by using countercurrent


what does the juxta-glomerular apparatus

maintains GFR in face of increases or decreases in blood flow to the kidney
macula densa senses tubular flow


what does the macula densa produce when there is an increase in tubular flow

adenosine which causes afferent arteriolar constriction


if there is a reduced tubular flow...

sensed by macula densa which causes granular cells to produce renin


reasons for reduced sensed volume

extracellular fluid depletion haemorrhage
pump failure


Kidney response to reduced sensed

•Efferent glomerular arteriolar constriction preserves
waste excretion
• Avid tubular sodium and water re-absorption
preserves extracellular fluid volume
net effect
- oliguria
- concentrated urine
- low urine Na concentration
- high urine potassium secretion


what helps maintain extracellular fluid calcium concentration

sensing tissues - parathyroid gland

calciotropic hormones - parathyroid hormone , hydroxylated vitamen D

effector tissues - kidney , intestine and bone


equation for clearance

= number of particles in urine /concentration of particles in plasma


what is creatinine

normal product of muscle metabolism
plasma concentration is dependent on muscle mass and kidney function
incompletely filtered but some tubular secretion


creatinine clearance

= (urine volume x creatinine concentration in urine )/ conc of creatinine in plasma


effect of muscle ,mass on the serum creatinine levels leads to ...

overestimation of function in women , elderly and other low muscle mass groups


what are the 3 concentric layers of connective tissue that protect and stabalise the kidnay?

fibrous capsule - layer of collagen fibres
adipose fat
renal fascia - dense fibrous outer layer that anchors the kidney into surrounding structures . the renal fascia also lines the renal sinus and internal cavity within the kidney


what is the hilum

is the entry of artery , renal nerves and exit of the vein and ureter


what is the difference between the cortical and juxtamedullary nephrons

85% Cortical nephrons & 15% Juxtamedullary nephrons
• Cortical nephrons are situated mainly in the cortex, they have a short loop that dips slightly into the medulla.
• Juxtamedullary nephrons have long nephron loops that extend deep into the medulla. The long loop plays a key role in water conservation and the formation of concentrated urine


the walls of the glomerular capillaries are covered in what?

podocytes which are specialised cells that create slits


what is the glomerular filtration barrier

endothelial cells
glomerular basement membrane


what is autoregulation

is the process by which the afferent arterioles respond to changes in pressure in the glomerulus by dilating or constricting (myogenic reflexes). This maintains the local pressure constant between 60-70mmHg.


juxtaglomerular apparatus is made up of

macula dense (specialised part of the DCT )
juxtaglomerular cells (produce renin )
mesengial cells


RAAS system

when blood volume falls
juxtaglomerlar cells secrete renin into blood stream
renin converts angiotensin I
ACE from lungs converts angiotensin I to II
ANG II causes sytemic vasoconstriction . increasing BP . Acts on the adrenal glad to produce aldosterone


what is atrial natriuretic peptide ANP

hormone released from the atria when blood volume is high . the increased venous return stretches the walls of the atria and releases ANP
causes dilation of the afferent arterioles and constriction of efferent , thus increasing GFR.
there is decreased reabsorption of sodium in the tubules


where is the majority of bicarbonate absorbed



characteristics of the thin descending loop

permeable to water but impermeable to sodium and other salts


characteristics of the thick ascending loop

actively pumps out sodium and chlorine but is impermeable to water


what is the osmolarity of the loop

The osmolarity of the loop and the surrounding interstitial renal space increases deeper into the medulla. Therefore, the deeper medullary parts of the kidneys are saltier. The base of the loop has an osmolarity of 1200 mOsm/L • Countercurrent


what is an overview of the counter current multiplication

1. Sodium and chloride are pumped out of the thick ascending limb and into the interstitial fluid.
2. This pumping action raises the osmotic concentration in the interstitial fluid around the thin descending limb.
3. This results in an osmotic flow of water out of the thin descending limb and into the peritubular fluid. This loss of water increases the solute concentration in the thin descending limb.
4. The arrival of the highly concentrated solution in the thick ascending limb speeds up the transport of sodium and chloride ions into the interstitial fluid of the medulla.


what does a NK2CL co transport do?

located on the apical membrane of the thick ascending limb . it transports 2 chloride ions , 1 sodium ion and one potassium ion by active transport .
the potassium can be recycled as it passively moves back down the conc gradient to the tubular lumen. the positive charge created by the potassium drives other ions to pass through the intracellular gaps.
this is targeted by loop diuretics like furosemide


how much of the primary filtrate reaches the DCT



what is an ENaC

epithelial sodium channel is unique protein that sits within the apical membrane of the principal cell and has affinity for sodium . sodium moves through the ENaC alone . the entry of sodium from the lumen creates a lumen negative voltage which stimulates the secretion of potassium ions into the lumen via apical channel


things to look out for in urinalysis

frothy urine - protein present
concentrated urine - dehydration
fishy smell - infection
sweat smell - ketones (DKA)
blood - visible haematuria and or non visible


what are the different types of calculi?

calcium oxalate (60%)
calcium phosphate (15%)
uric acid (10%)


symptoms of renal stones

continuous dull ache in loins


symptoms of ureteric stones

cause classic renal colic due to increase in peristalsis in ureters in response to passage of small stone - pain usually radiated from loin to groin


symptoms of bladder stones

cause strangury -urge to pass but cannot
recurrent untreatable UTIs , haematuria or renal failure


what are the different categories of transplant donation

directed donation - to a loved one or friend

non-directed - donor gives an organ the general pool of patients to be transplanted into the recipient and the top of the waiting list


where is erythropoietin made

in the kidney, the renal interstitial cells (fibroblasts) will sense hypoxia and are sensitive to low o2 levels and will start producing it


gold standard for measuring GFR

insulin is freely filtered by the glomerulus and neither reabsorbed not secreted by the tubule .
insulin clearance is the gold standard - but too expensive and cumbersome


why are creatinine and cystatin C used for measuring GFR

there is no such endogenous substance that is produced at a constant rate, that is freely filtered at the glomerulus , not reabsorbed and not secreted. but these two come very close


what is creatinine

• Normal product of muscle metabolism
• Daily production constant
• Plasma concentration dependent on muscle mass
and kidney function (and recent protein intake)
• Incompletely filtered but some tubular secretion


what is serum creatinine problems

exponential relationship leads to slow recognition of loss of the first 70% of kidney function . surprise at the sudden rise in creatinine

effect of muscle mass leads to ;
overestimation of fucntion in women and elderly and in other low musce mass groups


what is GFR measured in


eGFR by MDRD formula is based on serum
creatinine, age, sex and black race


How can we tell kidneys are not

• Low eGFR - <60ml/min
• Rise in serum creatinine within the
eGFR>60mL/min range


oliguria is a warning of what?

warning of impending acute
tubular necrosis


oliguria is a warning of what?

warning of impending acute
tubular necrosis
Kidney very sensitive to other ‘insults’ when
oliguric eg intravenous contrast, nephrotoxic
medicines, infection


causes of acute kidney infection or chronic kidney infection

ineffective blood supply
glomerular diseases
tubulo-interstitial diseases
obstructive uropathy


what threats are there to homeostasis

generation of CO2 from aerobic respiration

metabolism of foods generating acid or alkali

incomplete respiration - anaerobic - ketoacids and lactic acid

loss of alkali in stool or loss of acid in vomiting


acid base regulation has 3 major components

ventilation- control of co2
renal regulation of HCO3 and H+ secretion and reabsorption


change in H+ by factor of 2 leads to change in pH of



what are buffers

weak acids , partially dissociated in solution


what do buffers do?

buffers avoid big changes in hydrogen concentration

because co2 is highly diffusable and conc of co2 is regulated and controlled by respiration co2 conc is held constant
addition of H+ consumes HCO3 which generates co2 and water , the co2 is then exhaled and there is little h+.
loss of h+ leadz to the opposite , generating HCO3



IT can be eliminated from the body as a gas


How do the kidneys Regulate AcidBase

• Reabsorb filtered HCO3
• Secrete “fixed” acid
– Titrate non- HCO3 buffer in urine - primarily PO4
– Secrete NH4
into urine
• These goals are achieved by using selective permeability
of the luminal and baso-lateral cell membranes to match
transport of H+ and HCO3 in opposite directions


how is HCO3 reabsorbed

Active process largely in proximal tubule with
small contributions from TALH and DCT
• Inability to reabsorb filtered HCO3 is a cause of
metabolic acidosis


what does glutamate metabolism produce

bicarbonate and ammonia


excretion of acid in the kidneys

tubular cells generate new bicarbonate, which is absorbed, along with a hydrogen that binds ti a base other than bicarbonate . filtered PO4 or secretion of ammonia


excretion of ammonium is regulated by..

metabolism of glutamine . acidosis stimulates glutamine transport and oxidation .


metabolic acidosis

H+ increased
pCO2 decreased
HCO3 decreased


causes of metabolic acidosis

addition of extra acid - lactic acidosis , ketoacidosis

failure to excrete acid - renal tubular acidosis

loss of HCO3 - in stool or urine
* primary abnormality is fall in plasma HCO3
compensatory respinse is fall in pCO2 due to respiratory drive


Systemic effects of metabolic

• Arrythmias, ↓cardiac contractility, vasodilation
– Resp
• ↑ventilation (Kussmaul’s breathing)
– Metabolic
• Protein wasting, resorption of Ca from bone
– Other
• Neutrophilia


what is the main reason to calculate anion gap

is to identify likely cause
of metabolic acidosis – especially lactic acidosis, or
ingestion of acid

Normal AG: [Na+
] – {[Cl]
+ [HCO3
] = 6-12 mmol/

Difference between major cation (Na) and major anions –
- reflects presence of unmeasured anions


normal range of anion gap

9-16. BEWARE decrease in albumin can adjust anion gap by decreasing it by 2.5 for every 10g/L


metabolic alkalosis

decreased H+
increased HCO3
compensatory response increased pCO2


main causes of metabolic alkalosis

gastric acid loss - vomiting
volume depletion
bartters cushings
profound k depletion


respiratory acidosis

H+ decreased
HCO3 increased
pCO2 increased
compensatory response to retain HCO3
most of the H+ is buffered intracellularly with later renal compensation


respiratory alkalosis

H+ decreased
HCO3 decreased
pCO2 decreased
acute alkalosis increases the binding of Ca2+ to albumin thus inducing fall in ionised Ca2+ and tetany


venous a lymphatic drainage of bladder

surrounding bladder is a rich plexus of veins that ultimately empties into the internal iliac veins
lymphatics drain into vesical, external iliac , internal iliac and common iliac lymph nodes


bladder innervation - motor efferent parasympathetic fibres

SACRAL PREGANGIONIC nuclei in intermediolateral columns of S2,3,4


SYMpathetic motor innervation of bladder

pre ganglionic sympathetic nerve fibres arise from T10-12 and L1-2

travel in hypogastric nerves and innervate trigone /blood vessels of bladder and smooth muscle of prostate in men


gating theory

Afferent input into cord nullified by inhibitory
inter-neurones, restricting transmission to
preganglionic parasympathetic cell bodies
• Within parasympathetic ganglia inhibitory
effect of postganglionic sympathetic nerves
• Effect: Post-ganglionic parasymp fibres
‘protected’ from afferent input until
‘threshold’ reached


where does ONUF's nucleus lie

medial part of the anterior horn of the spinal cord


where is pontine micturition centre located

dorsolateral region of pons
recieves projections from cortex , cerebellum , brainstem and extrapyramidal system


what does the PMC do?

PMC nuclei sends axons , via lateral columns , to sacral micturition centre (both interomediolateral nucleus and ONUF's nucleus.
critical level of integration of storage and voiding


where is the PMC found (barringtons nucleus

found in dorsolateral region of pons


mechanism of Detrusor smooth muscle contraction

• NMJ transmission – increase in intracellular Ca++ :
• 1. Membrane depolarisation - voltage sensitive ion
channels – influx of extracellular Ca++
• 2. Ach binds to G-protein-linked (muscarinic) receptors
- release Ca++ from intracellular stores
• M2 receptors predominate in number, M3 in functional
• ‘Regions of close approach’ - functional syncitium


examples of neurological conditions associated
with abnormal bladder and sphincter function

– Spinal cord injury
– MS
– Neuropathic detrusor hyperreflexia eg in patients
with spina bifida
– Parkinson’s disease


what is spinal shock

period of decreased excitability at and below spinal cord injury
- absent somatic reflexes and flaccid muscle paralysis
- autonomic activity decreased
- acontractile areflexic bladder
-spincter = functioning
- retention
lasts days to months


reflex recovery from spinal shock

1st - striated muscle of pelvic floor
- return of bulbocavernosus reflex
- s3,4 pinch glans /clitoris or pull catheter and anal sphicter contracts on your finger
if BCR present ; sacral micturition centre is intact


autonomic dysreflexia

spinal cord injury T6 or higher (splanchic circulation = t6-10)
exagerated sympathetic activity in response to a stimulus below level of sci
potentially fatal.
increased BP , Decreased HR , sweating, flushing above lesion, vasocontriction below.


detrusor hyperreflexia

this is bladder overactivity in a patient with an underlying neurological condition sucha as MS or parkinsons
occurs in 70% following a stroke.
if bladder is very high it can result in upper tract dilation . mainstay of treatment is anticholinerics - M3 receptor blockerz . cholinergic - parasympathetic control
adrenergic control - sympathetic


bladder outflow obstruction

principle cause in men is prostatic hypertrophy
women - pelvic organ prolapse

neurological disease can cause relaxation of external sphincter
tumours , stones, strictures


what is verumontanum a landmark for

TURP as lies just proximal to external urinary sphincter
the verumontanum leads into the prostatic utricle and on either side of V is the opening of ejaculatory duct.


chronic retention

• Painless retention of >300ml
• Broadly subdivided into 2 groups
– HPCR – residual volume remains at a pressure
higher than the intra-abdominal pressure after
• HPCR associated with bilateral hydronephrosis


Pathophysiology of upper tract
dilatation in chronic retention

Combination of diuresis and
bladder filling causes upper
tract pressures to rise
Once ureters become dilated,
co-aptive peristalsis is lost and
ureteric drainage becomes
dependent on gravity
If end void pressure >25cm/H2O,
deterioration in renal function
HPCR associated with
hypertension (50%)
Peripheral oedema
CCF (20%)


what changes occur during the period of obstruction

reduction in GFR , secondary increase in the fractional excretion of solutes and water in an attempt to compensate.->
with extremes of dietry intake of salt and water and reduced ability of the nephron to compensate->
salt and water retentipn are common ->
hypertension , peripheral oedema , CCF


post obstructive diuresis

Refers to marked polyuria that occurs
after relief of BUO or obstructed single kidney
May be physiological - to excrete retained
water and solutes
Or pathological caused by impaired sodium
reabsorption or concentrating ability.


what are the two stages of post obstructive diuresis

tubular 0-14 days
reversal of tubular changes in obstruction - increased fractional excretion sodium leads to diuresis

glomerular 14-3month
gradual and more subtle


Why does diuresis occur

Patients with prolonged diuresis are
unresponsive to ADH (acquired DI)
Prolonged impairment of sodium
Elevated levels of ANP


Clinical management of post
obstructive diuresis

20% patients urine output > 4litres/day
10% patients develop thirst requiring oral fluids
5% patients require i.v replacement therapy
because of postural hypotension
1% patients prolonged POD/ chronic salt losers


management of post obstructive diuresis

Strict hourly urine output
Daily weights,
BP - look for orthostatic hypotension
Majority do not need volume
replacement i.e. diuresis is physiological
A minority of patients will show a UO
of > 200ml/hr for 6 hours
These patients need close observation
and fluid replacement
Aim to replace 1/2 hourly urine output
with N. saline
Also watch for postural hypotension
and hyponatraemia


respiratory alkalosis

• ↓ CO2 due to Hyperventilation leads to ↓ [H+] • Compensatory Mechanism:
• Renal compensation - H+ ions are generated and HCO3- ions are secreted.
• Respiratory compensation - stimulation of arterial and CSF chemoreceptors causes a decrease in breathing rate


respiratory acidosis

• ↑ CO2 due to Hypoventilation leads to ↑ [H+] • Compensatory Mechanism: • Most of the increased [H+] is buffered intracellularly • Renal compensation - H+ ions are secreted and HCO3- ions are reabsorbed more. • Respiratory compensation - stimulation of arterial and CSF chemoreceptors causes an increase in breathing rate


sites of bicarbonate reabsorption

90% in PCT , 10% in intercalated discs of DCT / collecting duct


how is a fixed acid buffered

via the excretion of hydrogen ions in the form of ammonia and phosphate and subsequent absorption of bicarbonate


volatile acids

can be eliminated from the body as a gas



Dilation of the renal pelvis and calyces - progressive atrophy of the kidneys, thus leading to kidney impairment