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Flashcards in FUNCTIONS OF THE KIDNEY Deck (102):
1

functions

-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)

2

How much of the cardiac output goes to the kidneys

20%

3

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

4

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

5

Normal GFR approx

100ml/min = 144L per day

6

movement of solutes and water across membranes ..

diffusion

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

controlled by systemic and local mediators

7

PCT cell features

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

8

how much sodium chloride is reabsorbed in PCT

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

9

what are the loop of henle rules

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

10

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

11

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

adenosine which causes afferent arteriolar constriction

12

if there is a reduced tubular flow...

sensed by macula densa which causes granular cells to produce renin

13

reasons for reduced sensed volume

extracellular fluid depletion haemorrhage
vasodilation
pump failure

14

Kidney response to reduced sensed
volume

•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

15

what helps maintain extracellular fluid calcium concentration

sensing tissues - parathyroid gland

calciotropic hormones - parathyroid hormone , hydroxylated vitamen D

effector tissues - kidney , intestine and bone

16

equation for clearance

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

17

what is creatinine

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

18

creatinine clearance

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

19

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

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

20

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

21

what is the hilum

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

22

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

23

the walls of the glomerular capillaries are covered in what?

podocytes which are specialised cells that create slits

24

what is the glomerular filtration barrier

endothelial cells
glomerular basement membrane
podocytes

25

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.

26

juxtaglomerular apparatus is made up of

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

27

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

28

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

29

where is the majority of bicarbonate absorbed

PCT

30

characteristics of the thin descending loop

permeable to water but impermeable to sodium and other salts

31

characteristics of the thick ascending loop

actively pumps out sodium and chlorine but is impermeable to water

32

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

33

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.

34

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

35

how much of the primary filtrate reaches the DCT

15-20%

36

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

37

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

38

what are the different types of calculi?

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

39

symptoms of renal stones

continuous dull ache in loins

40

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

41

symptoms of bladder stones

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

42

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

43

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

44

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

45

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

46

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

47

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

48

what is GFR measured in

ml/min/1.73m2

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

49

How can we tell kidneys are not
working?

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

50

oliguria is a warning of what?

warning of impending acute
tubular necrosis

51

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

52

causes of acute kidney infection or chronic kidney infection

ineffective blood supply
glomerular diseases
tubulo-interstitial diseases
obstructive uropathy

53

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

54

acid base regulation has 3 major components

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

55

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

0.3

56

what are buffers

weak acids , partially dissociated in solution

57

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

58

WHAT IS A VOLATILE ACID

IT can be eliminated from the body as a gas

59

How do the kidneys Regulate AcidBase
Balance?

• 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

60

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

61

what does glutamate metabolism produce

bicarbonate and ammonia

62

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

63

excretion of ammonium is regulated by..

metabolism of glutamine . acidosis stimulates glutamine transport and oxidation .

64

metabolic acidosis

H+ increased
pCO2 decreased
HCO3 decreased

65

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

66

Systemic effects of metabolic
acidosis

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

67

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 –
Cl,
HCO3
-
- reflects presence of unmeasured anions

68

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

69

metabolic alkalosis

decreased H+
increased HCO3
compensatory response increased pCO2

70

main causes of metabolic alkalosis

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

71

respiratory acidosis

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

72

respiratory alkalosis

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

73

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

74

bladder innervation - motor efferent parasympathetic fibres

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

75

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

76

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

77

where does ONUF's nucleus lie

medial part of the anterior horn of the spinal cord

78

where is pontine micturition centre located

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

79

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

80

where is the PMC found (barringtons nucleus

found in dorsolateral region of pons

81

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
importance
• ‘Regions of close approach’ - functional syncitium

82

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

83

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

84

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

85

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.

86

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

87

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

88

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.

89

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
micturition
– LPCR
• HPCR associated with bilateral hydronephrosis

90

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
ensues
HPCR associated with
hypertension (50%)
Peripheral oedema
CCF (20%)

91

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

92

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.

93

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

94

Why does diuresis occur

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

95

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

96

management of post obstructive diuresis

Strict hourly urine output
Daily weights,
U+E’S
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

97

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

98

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

99

sites of bicarbonate reabsorption

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

100

how is a fixed acid buffered

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

101

volatile acids

can be eliminated from the body as a gas

102

hydronephrosis.

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