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Urinary > 3 > Flashcards

3 Flashcards

1
Q

What are four functions of the kidney?

A
  • Regulation: controls concentrations of key substances in ECF
  • Excretion: excretes waste products
  • Endocrine: synthesis of renin, erythropoietin, prostaglandins
  • Metabolism: active form of vitamin D, catabolism of insulin, PTH calcitonin
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2
Q

What is the basic principle of kidney in terms of things that are filtered and recovered?

A
  • over 99% of filtered water is recovered (blood)
  • Overy 99% of filtered sodium and chloride ions recovered (ECF)
  • 100% of bicarbonate recovered (mainly in PCT)
  • 100% of glucose and AA recovered in PCT
  • just a few waste products not recovered
  • some substances (ex. H+ secreted, so lose more than filtered)
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3
Q

What is ultrafiltrate?

A
  • filtered ECF

- contains water, ions all small molecules

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4
Q

How much fluid does the kidney filter?

A

180L/day: every L filtered over 10 times a day

  • recovers nearly everything
  • leaving on average about 1.5L per day of urine
  • kidney directly affects ECF but not ICF
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5
Q

What is the predominant ion cation and anion in ECF?

A
  • cation: sodium
  • anion: chloride
  • potassium is an important cation
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6
Q

What are the electrolyte compositions of the ICF and ECF?

A

-ICF: high K+, low Na+, many large organic anions

ECF: low K+, high Na+, main anion Cl- and HCO3-

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7
Q

How does water move during filtration?

A
  • thrugh osmotic forces
  • osmolality: solutes per kg of solvent
  • osmolarity: number of osmole of solute per litre
  • measured in milliosmoles
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8
Q

Describe the glomerulus as a filter

A
  • each glomerulus in each neurone contains afferent and efferent arteriole
  • found only in the cortex
  • 20% of blood from renal artery is filtered at any one time
  • 80% of blood arriving exits via efferent arteriole (unfiltered)
  • small tuft of capillaries surrounded by several layers of fenestrated and leaky epithelium
  • help to provide a selective filtration barrier and direct filtered fluids
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9
Q

Why is the diameter of the afferent arteriole slightly greater than the diameter of the efferent arteriole?

A
  • hydrostatic pressure of blood inside glomerulus is increased due to the difference in diameter of the incoming and outgoing arterioles
  • increased hydrostatic pressure helps to force certain components of the blood out of the glomerular capillaries
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10
Q

What is the filtration factor?

A
  • represents the proportion of fluid reaching the kidneys that passes into the renal tubules
  • normally about 20%
  • FF= GFR/RPF
  • GFR: about 125ml/min
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11
Q

Which type of nephron has autoregulation?

A

Cortical nephrons

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12
Q

What are the components of the renal corpuscle?

A
  • Bowman’s capsule and Bowman’s space
  • DCT and PCT
  • JG apparatus
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13
Q

What is the renal afferent arteriole?

A

-arteriole through which blood enters the glomerular capillaries

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14
Q

What are the glomerular capillaries?

A

-small tuft of inter-connecting capillaries with a fenestrated endothelium and specialized basement membrane known as the glomerular basement membrane which is involved in selective filtration of blood

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15
Q

What are podocytes?

A
  • specialized type of epithelial cell which directly invests the glomerular capillaries and are critical for the selectivity of glomerular filtration
  • contacts the glomerular BM using thin outpouchings known as “foot processes” that are close to one another
  • narrow spaces between the foot processes form a thin slit sometimes known as the “slit diaphragm” (filtration slits)
  • foot processes wrap around the outside of the loop of the capillary
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16
Q

What are renal efferent arterioles?

A

-vessels through which blood exits the glomerular capillaries

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17
Q

What is Bowman’s capsule?

A
  • layer of epithelial cells that surround the glomerular capillaries and is continuous with the epithelium of the proximal tubule
  • fluid filtered through the glomerular capillaries is thus directed into the proximal tubule by the Bowman’s capsule
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18
Q

What is Bowman’s space?

A
  • refers to the space between Bowman’s capsule and the glomerular tuft
  • where the ultrafiltrate goes before it leaves the convoluted tubules
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19
Q

What is mesangium?

A
  • basement membrane-like matrix in which the glomerular capillaries are embedded and which provides them structural support
  • Mesangial cells live within the mesangium and maintain this matrix
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20
Q

Describe the juxtaglomerular apparatus

A
  • endocrine structur consisting of macula densa
  • macula densa located in DCT and are known as “salt sensors”, help to communicate with glomerulus, afferent and efferent arteriole
  • macula densa affects renin release
  • renin is secreted when NaCl concentration in the filtrate decreases
  • Extraglomerular mesangial cells are connected to each other and to JG cells by gap junction
  • process of filtration is metabolically very demanding so o2 consumption of kidneys is high, needs constant blood flow
  • PCT has a brush border with narrow lumen while DCT has a very wide lumen
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21
Q

Describe the filtration barrier

A
  • made of 3 layers
  • from in to out
  • endothelial layer: closest to capillaries, very fenestrated
  • basement membrane: contains acellular gelatinous layer of glycoproteins which have a negative charge
  • podocytes layer
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22
Q

How does size affect the perm-selectivity of the barrier

A
  • if molecular weight is 5200 or greater, then it cannot fit into glomerulus
  • ex: inulin, hb, and serum albumin are too big
  • small molecular weight and effective radius less than 1.48nm will pass through
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23
Q

How does charge affect filtration?

A
  • since BM has a negative charge, it will repel molecules with negative charge
  • if molecule is large but has a positive charge it can get through barrier
  • if molecule is small but has a negative charge then it will be unable to get through barrier (ex. Proteins)
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24
Q

What is proteinuria?

A
  • when protein ends up in urine
  • in many disease processes the negative charge on the filtration barrier is so lost so proteins are more readily filtered
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25
Q

What are the three mechanisms of tubular reabsorption?

A
  • osmosis
  • diffusion
  • active transport
26
Q

Describe tubular reabsorption

A
  • majority of GF solution is reabsorbed in PCT
  • reabsorption is an energy demanding process
  • most energy is spent on sodium reabsorption since reabsorption of other things is coupled to the active transport of sodium ions
  • occurs with help of symporters on the apical membrane
  • symporters are depended on the 3Na-2K-ATPase located on the base lateral membrane
  • solutes are selectively moved from GF to the plasma by active transport
27
Q

What are the pressures in filtration? Describe them

A
  • Pgc: hydrostatic pressure in the capillary; regulated; large amount of pressure pushing on Bowman’s capsule
  • Pbc: hydrostatic pressure in Bowman’s capsule; pressure of water pushing against glomerulus capillary; opposes Pgc
  • piegc: oncotic pressure difference between capillary and tubular lumen; opposes Pgc but oncotic proteins are located in glomerulus; opposing force since they dont want water to leave however Pgc is greater so water will leave
  • opposing forces to Pgc allows for net filtration pressure
  • concentration of oncotic proteins will increase in efferent arteriole since water has left, this is important for reabsorption
28
Q

Explain the regulation of Pgc

A

-as BP rises so does hydrostatic pressure
-autoregulation helps to maintain GFR by maintaining Pgc
-as Pgc increases so does GFR and vice versa
-As BP increases, afferent arteriole constricts so GFR is unchanged
As BP decreases, afferent arteriole dilates so GFR is unchanged
-smooth muscle in arteriole responds to changes in vascular wall tension (auto-regulatory mechanism)
-occurs rapidly (3-10s)
-myogenic response

29
Q

How would we decrease GFR?

A

-constrict afferent arteriole and dilate efferent arteriole

30
Q

How would we increase GFR?

A

-dilate afferent arteriole and constrict efferent arteriole

31
Q

Explain tubuloglomerular feedback

A
  • further autoregulation
  • links sodium and chloride concentration at the macula densa with control of renal arteriolar resistance
  • macula densa cells in the ascending limb sense an increase in GFR, so contract afferent arteriole, decrease in Pgc, RPF, and ultimately GFR
  • acts in response to acute perturbations in the delivery of fluid and solutes to the JGA (or granular cells)
  • has 2 components: afferent arteriole resistance, efferent arteriolar feedback (hormonal)
  • controls the distal solute delivery and hence tubular reabsorption
32
Q

Explain tubular secretion

A
  • involves substances being added to glomerular filtrate in nephron tubule
  • removes excess quantities of certain dissolves things like H+ ions to maintain blood PH
  • substances that are secreted: K+, H+, ammonium ions, creatinine, urea, some hormones and drugs
  • process occurs from epithelial cells that line the renal tubules and collecting ducts into the glomerular filtrate
33
Q

Explain TG feedback if GFR increases

A
  • increased NaCl delivery into DCT lumen causes NKCC2 transporter to move more ions into the macula densa cells
  • increased intracellular conc. Of NaCl ions triggers the release of ATP
  • ATP leaves MD cells through exit channels
  • once ATP leaves it is quickly converted to AMP and then to adenosine
  • adenosine binds to A1 receptor which is located on the mesangial cells of afferent arteriole
  • leads to activation of G proteins (ICPP)
  • increases intracellular calcium spreads to mesangial cells and smooth muscle cells via gap junctions
  • the increase causes constriction resulting in vasoconstriction of afferent arteriole
  • ultimately reducing Pgc and GFR
  • increase also inhibits renin release in JG
  • goal: to decrease GFR
34
Q

Explain TG feedback if GFR decreases

A
  • prostaglandin release from MD cells to vasodilate afferent arteriole
  • would result in increases plasma entering glomerulus which will increase Pgc and increase GFR
35
Q

What medications can decrease GFR and why?

A
  • NSAIDS because they inhibit prostaglandins

- ACE inhibitors as they will constrict the efferent arteriole

36
Q

Explain the neural regulation of GFR

A
  • sympathetic nerve fibres innervate AE and EA
  • normally sympathetic innervation is low (no effect of GFR)
  • fight or flight, ischaemia, or haemorrhage can stimulate renal vessels
  • vasoconstriction occurs as a result which conserves blood volume (haemorrhage) and can cause a fall in GFR
  • parasympathetic release of NO for endothelial cells and vasodilation
37
Q

Explain the glomerulotubular balance

A
  • glomerulus and PCT in balance
  • autoregulation of GFR prevents it from changing too much
  • 1st line of defence: Myogenic and TG feedback
  • 2nd line of defence: glomerultubular balance which blunts sodium excretion response to any GFR changes which do occur despite 1st line responses
38
Q

What is the normal GFR?

A

90-120mL/min/1.73m(squared)

39
Q

What factors is GFR dependent on?

A
  • age
  • gender (female lower than male since F are smaller)
  • size of individual
  • size of kidneys
  • pregnancy
40
Q

Explain how age affects GFR

A

Babies
-nephron development finished by 35-36th week of fetal development
-premature and LBW infants often have lower nephron numbers
-fetal excretion predominantly via placenta
-at birth GFR: 20ml/min
-normal GFR by 18 months age
Old
-GFR starts declining after 30 years
-rate of decline is 6-7ml/min per decade
-loss of functioning nephrons
-some compensatory hypertrophy (by increasing kidney and nephron size)

  • as renal cortex increases so does glomerulus size meaning GFR increases
  • as renal cortex volume decreases, medulla tries to compensate by increasing
  • despite kidney trying to compensate, it overall decreases in size as you age
41
Q

How does pregnancy affect GFR

A
  • GFR increases 50% (130-180ml/min)
  • kidney size increases
  • increases fluid volume (vascular and interstitial)
  • nephron number the same (no further nephrogenesis)
  • back to pre-pregnancy levels 6 months post-part I’m
  • water in body increases so ECF increases
42
Q

Explain how disease affects GFR

A
  • decrease in GFR in a pt. Means kidney function has worsened
  • decline in number of nephrons
  • decline in GFR within individual nephrons
  • increase in GFR means kidney function has recovered
  • when kidney function declines slowly, individual nephrons may hypertrophy so actual GFR may not fall until significant kidney damage has occurred
43
Q

What is clearance?

A

-volume of plasma cleared of a substance per unit of time where substance is denoted as X
-C(x)=A(x)/P(x)
C= clearance (ml/min)
A=amount of substance eliminated per unit time (mg/min)
P=plasma concentration of substance (mg/ml)
-clearance from the body, not just kidneys
-looking at the amount of plasma body needs to get rid of substance x
-look at diagrams

44
Q

What properties does the ideal substance to measure renal clearance need?

A
  • freely filtered across glomerulus
  • no secretion by renal tubule
  • no reabsorption by renal tubule
  • if these factors are true, then the amount of substance X excreted in urine per min is equal to the amount filtered by kidney per min
  • excretion rate=GFR
45
Q

How do you calculate excretion rate?

A

Excretion rate= U (amount in urine) x V (urine flow rate)

46
Q

If GFR equals excretion rate how would we calculate it?

A

C(x)= [Ux x V]/Px

47
Q

If flow increases, what would happen to renal clearance?

A

It would increase

48
Q

If plasma concentration increases, what would happen to renal clearance?

A

It would decrease

49
Q

What is the gold standard for measurement of renal clearance and why?

A
  • inulin: plant polysaccharide that is ingested into the body
  • inulin clearance is a surrogate for GFR
  • but is not produced at a constant rate
  • look at two formulas
50
Q

Why dont we use inulin as a measurement?

A
  • requires continuous IV injection to maintain steady state

- requires catheter and timed urine collections

51
Q

What other substance (radioactive) could we use to measure renal clearance and why?

A

51 Cr-EDTA

  • radioactive labelled marker
  • cleared exclusively by renal filtration
  • timed injection with blood samples taken 2, 3, 4 hours afterward
  • just need to give one shot
  • no need for urine sample
  • 10% lower clearance than inulin
  • used clinically in children and those who need kidney transplant
  • used in cancer patients as well since many cancer treatments are nephrotoxic
  • since radioactive pt. Needs to stay some time after injection to ensure no radiation
52
Q

Explain how creatinine is used as an endogenous measurement of kidney function

A
  • end product of muscle breakdown
  • meets all criteria but not produced at a constant rate
  • production of creatinine is different in all individuals, dependant on various factors
  • creatinine clearance is an overestimate of GFR
  • measured by urine creatinine over 24hrs and serum creatinine
  • disadvantages: tedious, frequently inaccurate, overestimate
  • used in pregnancy
53
Q

What factors affect creatinine levels?

A
  • food intake
  • muscle mass
  • renal filtration, secretion and excretion
  • age
  • gender
  • ethnicity
  • certain drugs
54
Q

What is the relationship between serum creatinine and GFR?

A
  • inversely proportional to one another but relationship is not linear
  • under stable conditions serum creatinine stays stable in an individual but it can reflect very different GFR in different people
  • easy to measure with creatinine but very variable
55
Q

What is eGFR and what are the two types?

A

-estimated GFR (best guess)

MDRD eGFR and CKD-EPI

56
Q

Describe MDRD eGFR

A

4-variable equation (serum creatinine, age, sex, white or black)
-standardized to body surface area of 1.73 m(square) so no need for pt. Height and weight
inaccurate in:
-people without kidney disease (ex. Transplant donors)
-children
-pregnancy
-old age
-other ethnicities
-amputees/reduced muscle mass
-pt’s with higher levels of kidney function

57
Q

Describe CKD-EPI

A
  • uses same variables as MDRD calculation but calculation is slightly different (more diverse background)
  • as accurate as MDRD when eGFR <60ml/min
  • more accurate when eGFR>60ml/min
58
Q

Why is eGFR less accurate with mild kidney disease?

A
  1. Reduction in GFR (ex. If glomerular surface area reduced, causes increase in blood flow)
  2. Reduced nephron number leads to nephron hypertrophy so no changes in GFR
  3. Reduced filtration of creatinine (due to reduced GFR) results in increased serum creatinine and increased secretion into the tubule (in order to maintain steady state of serum creatinine)
59
Q

A patient has a GFR measured from the inulin clearance of 125ml/min. Plasma creatinine is 0.01 mg/ml. Urine flow rate is 1ml/min and the conc. Of creatinine in her urine is 1.35mg/ml. What is the rate of filtration of creatinine in the glomerulus?

A

125(0.01) = 1.25 mg/min

60
Q

A person has a urine flow rate of 1ml/min; plasma inulin is 8.33 mg/100ml; plasma creatinine is 2mg/100ml; urine inulin is 10mg/ml; urine creatinine is 2.6mg/mL. Calculate the rate of creatinine secretion?

A

Rate of secretion is 2.6 mg/min
EGFR= (Uin x V)/Pin (10 x 1)/0.0833= 120ml/min
120ml/min x plasma creatinine (0.02)= 2.4 mg/min
2.6-2.4= 0.2 mg/min

Urinary (11 decks)

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