Renal Excretory function

Question 1

what is the glomerulus made up of

Answer 1

• endothelium of capillaries - these are fenestrated
• basement membrane
• epithelium of the bowman capsule that contains podocytes (these have gaps between them)

Question 2

what are the factors that determine the filtrate

Answer 2

• Net filtration pressure
• Podocyte slit pores
• Size of molecular
• Charge of molecule

Question 3

what is allowed to diffuse through the glomerulus

Answer 3

– Water
– Electrolytes eg Na, K, Cl, phosphate, glucose
– Urea, amino acids

Question 4

what is the molecular weight cut off by the basement membrane

Answer 4

– MW cut off of 5200 daltons
– MW of albumin is 69,000 daltons - therefore albumin is usually not in the urine as it cannot get through the basenent membrane

Question 5

what is the difference between the afferent and efferent blood vessels

Answer 5

• afferent has a larger diameter than efferent

- afferent brings blood in whereas efferent removes the blood

Question 6

what is the filtration fraction

Answer 6

it is normally 20%
- this is the proportion of the blood plasma that is filtered through glomerulus into the bowman capsule which enters in the proximal tubule

Question 7

What happens to podocytes in renal disease

Answer 7

• in renal disease - the podocytes become inflamed and enlarged therefore the gaps between them get larger which enables more solutes to enter the urine
• proteinuria is therefore a sign of glomerular inflammation

Question 8

what is the normal physical pressure in the glomerular capillaries and wha tis the net pressure

Answer 8

= normal physical pressure is 55mmHg

= net pressure 10mmHg

Question 9

define the glomerular filtration rate

Answer 9

• this is the total amount of fluid filtered through all the glomeruli in both kidneys
• usually 120-125 ml/min

Question 10

what is the renal plasma flow

Answer 10

• 680 ml/min

Question 11

what is used clinically to assess the health of the kidney

Answer 11

GFR

Question 12

how do you measure GFR

Answer 12

• Measured by clearance (of creatine)

Question 13

what is clearance

Answer 13

it is the effective volume of plasma completely cleared of a substance per minute

Question 14

write dow the formula for clearance

Answer 14

clearance = urine concentration x urinve volume/ plasma concentration

Question 15

what do you need to measure the clearance of a substance

Answer 15

1. measure the concentration of the creatine in the plasma
   2, collect urine for a fixed period to get the urine flow (ml/min)
   3, measure the concentration of creatinine in the collected urine

Question 16

if 100% blood component is filtered through the glomerulus ..

Answer 16

• this means that material goes into the proximal tubule at the same rate as the water in the plasma, therefore the clearance of the substance will be the same as the glomerular filtration rate which is 125 ml/min

Question 17

if 100% of the blood component is filtered through the glomerulus and all of it is reabsorbed ..

Answer 17

• no blood will be cleared of the material

- clearance is o

Question 18

that 100 % of the material is filtered and in addition all of the material in the efferent arteriolar blood is secreted into the urine

Answer 18

• renal venous blood will have no material in it and all the blood passing through the kidney will have been cleared of the material
• the clearance will then equal the renal plasma flow

Question 19

what can clearance be equal to

Answer 19

Not removed at all by kidney: Clearance = zero

Removed at same rate as water passes through glomeruli: Clearance = GFR

Completely removed from blood passing through kidney: Clearance = RPF

Question 20

what do you use to measure clearance

Answer 20

• inulin - completely filtered from the plasma and is not reabsorbed, have to iV inulin over a period of hours until you reach a steady plasma concentration - not clinically practical as it takes too long
• Clinically use creatinine to measure GFR, produced naturally by the Body and is filtered by the glomerulus and is also secreted by the peritubular capillaries in the small amounts, it is already at a steady state concentration in the blood so it takes much shorter to measure

Question 21

what does the secretion of creatinine by the peritubular capillaries do

Answer 21

• means that the creatinine clearance overestimates the GFR by 10-20%

Question 22

how do you measure eGFR

Answer 22

MDRD

Question 23

what is the equation of MDRD

Answer 23

eGFR (ml/min per 1.73m2) = 185 x creatine/88.4)-1.154 x age-0.203 x (0.742 if female)x 1.210 if black

Question 24

what do you need for MDRD

Answer 24

CAGE

• creatine
• age
• sex(gender)
• ethnicity

Question 25

why is eGFR more important | than creatine for measreuemtn

Answer 25

eGFR is more important than creatine as you want to known what happens when someone develops acute kidney injury as this can result in small changes in serum creatine but big changes in eGFR

Question 26

what does the creatinine levels also depend on

Answer 26

Muscle mass - increase in muscle mass increase in the amount of creatine Body size - means more muscle mass Sex and race

Question 27

what are the 3 structures of the juxtaglomerular apparatus

Answer 27

- afferent arteriole - efferent arteriole - distal tubule

Question 28

what lines the wall of the distal tubules

Answer 28

- macula densa

Question 29

what are macula densa

Answer 29

- sodium sensors | - release local chemicals which modulate the contraction of smooth muscle around the afferent arteriole

Question 30

why does a low sodium level indicate a low GFR

Answer 30

Sodium is removed (by reuptake) from the proximal tubule at a fixed rate. If the flow is slow (low GFR) , more sodium has been removed by time the fluid has reached the end of the tubule and the remaining concentration will be low . Conversely, if the flow is fast (high GFR) , more sodium is flowing past the uptake sites than they can manage, so the concentration remains high. With low distal tubule sodium, the macula densa cells release local chemical factors which relax the smooth muscle in the afferent arteriole, thus increasing the filtration pressure and increasing GFR. Conversely, if the sodium level is too high, the macula densa cells release chemical factors which constrict the the afferent arteriole, decrease filtration pressure and reduce GFR.

Question 31

name a drug that inhibits tubular secretion of creatinine

Answer 31

Some drugs inhibit tubular secretion of creatinine (eg Trimethoprin), leading to a raised plasma creatinine even though GFR may be unchanged

Question 32

what is apical and basolateral

Answer 32

Apical – this is facing the tubules | Basolateral is facing the peritubular capillary and interstitial

Question 33

are there gaps between tubular cells

Answer 33

There are no gaps between tubular cells unless they are tight junction this restricts flow from the tubular lumen to the intersititum

Question 34

what do the tight junction do

Answer 34

limits water and solute and movement between cells, they maintain polarity and allow different transport proteins in the basolateral versus the apical

Question 35

what are the mechanisms of solute transport and give examples

Answer 35

• Passive – Passive diffusion • Down a concentration and electrochemical gradient – Carrier mediated (facilitated) diffusion • Carrier proteins • Selective – Diffusion through membrane channel ``` • Active – Movement of solutes against an electrochemical gradient – Dependent on ATP – Examples • Sodium pump ( Na-K ATPase) • H+-ATPase (distal nephron) • Ca +2 -ATPase ```

Question 36

describe how proximal convoluted tubule does trnaposrt

Answer 36

- Most important part is the sodium potassium ATPase on the basolateral membrane - this pumps 3 sodium into the interssitum and 2 potassium into the tubular cell - this requires ATP to work therefore it is primary active transport - This drives everything else that happens within the tubular lumen, tubular cells and insterisititum - This maintains different concentrations intracellular and extraceullar - low sodium inside the cell, whereas high potassium inside the tubular cell - Glomerulus pumps everything into the tubular lumen therefore the sodium concentration in the tubular lumen is high compared to the intracellular tubular cell due to the Sodium potassium ATPase - Therefore the sodium, phopshate, glucose and amino acids pass along a gradient into the tubular cells this is seocndary active transport as this is due to the sodium and potassium ATPase - Urea on the other hand oves passively diffusion

Question 37

what happens if there is mutation in the sodium potassium ATPase on the basolateral membrane

Answer 37

you die - don't survive

Question 38

what active transport does the sodium potassium ATPase work by

Answer 38

primary active transport

Question 39

what happens if there are defects in the apical sodium/cysteine cotransporter

Answer 39

cystinuira | – Autosome recessive. Abnormal cystine excretion – resulting in recurrent cystine renal stones

Question 40

what happens if there are defects in the apical Na/glucose cotransporter

Answer 40

renal glycosuria - abnormal urinary glucose loss. - Happens despite normal/low blood glucose

Question 41

what happens if there is a defect in the basolateral sodium bicarbonate

Answer 41

proximal renal tubular acidosis Type 2 renal tubular acidosis. A classic course would be Fanconi’s syndrome (along with glycosuria, amino aciduria, phosphaturia, glycosuria, bicarbonaturia)

Question 42

what happens if there is a defect with the apical Na/Cl/K in the thick ascending loop

Answer 42

• Bartter’s type 1 mimic of the effects of furosemide. causes - Hypokalaemia, - metabolic alkalosis, - hypocalcaemia, - hypomagnasaemia

Question 43

what happens if there is a defect in the apical sodium chloride con transporter in the distal tubule

Answer 43

• Gitelman’s: - Mimic of thiazide use. causes - Hypokalaemia, - metabolic alkalosis, - hypomagnasaemia, - hypercalcaemia

Question 44

name some proximal tubule defects

Answer 44

- Apical Na/cysteine cotransorpter = cystinuria - Apical Na/glucose cotransporter = renal glycosuria - Basolateral Na/HCO3 = proximal RTA

Question 45

what does the proximal tubule have that increases its surface area

Answer 45

– Apical brush border (microvilli), this causes a Large surface area

Question 46

what is the function of the proximal tubule

Answer 46

– Bulk of reabsorption of solutes – up to 80% – Water – up to 65% – Amino acids, low molecular weight proteins – up to 100%

Question 47

what is the aim of the loop of Henle

Answer 47

- to reduce the amount of water present in the urine

Question 48

how does the loop of Henle work

Answer 48

- descending loop of Henle is permeable to water and solutes so they can move in and out - thick ascending loop of Henle is impermeable to water but can do active transport of sodium 1. Fluid flows from the proximal tubule down into the thin descending loop of Henle 2. - as the fluid descends in the tubule it becomes more concentration because it is in equilibrium with the high concentration in the extracellular fluid in the renal medulla 3. this then goes up into the thick part of the ascending limb 4. the thick part is impermeable to water but it has membrane pumps that move sodium and chloride ions out into the extracellular space by active transport 5. this maintains the high extracellular fluid concentration in the renal medulla 6. when the fluid leaves the loop of Henle it enters the distal tubule 7. the fluid entering the distal tubule is more dilute than the plasma due to the removal of sodium and chloride

Question 49

how much water does the loop of Henle reabsorb

Answer 49

- Important in reabsorbing 30% of water that enters the loop of Henle

Question 50

what is the difference in osmolaitiy in the ascending and descending loops of heel

Answer 50

There is therefore a difference in osmolality in the ascending and descending loops of around 200 mOsm at any one time

Question 51

as the urine travels up the ascending loop of Henle it ...

Answer 51

As the urine travels up the TALH, it reaches the same concentration that it was at the point where it enters the loop. Thus, urine volume is decreased but solutes are preserved

Question 52

why do we have a counter current mechanism

Answer 52

– Filtrate that leaves the proximal tubule is iso-osmolar to plasma – In the event of excess water overload, excretion of urine is required that is hypo-osmolar to plasma (i.e dilute urine) – In the event of water restriction, hyper-osmotic urine excretion is required (concentrated urine)

Question 53

what provides the counter current mechanism

Answer 53

- the vasa recta provide a countercurrent exchange mechanism to preserve the concentration gradient despite a blood flow through the vasa recta capillaries

Question 54

the longer the loop of Henle...

Answer 54

The longer the loop of Henle the greater the countercurrnet multiplier system therefore the more water reabsorbed and a more concentrated urine

Question 55

describe what solutes are transporter in the ascending limb

Answer 55

– Secondary active transport of Na, K and Cl in thick ascending limb – Paracellular transport of Na, Ca and Mg down a electrochemical gradient

Question 56

what does the distal nephron consist of

Answer 56

– Distal tubule – Connecting tubule – Collecting duct (cortical and medullary)

Question 57

what is the function of the distal nephron

Answer 57

– K excretion – Regulation of sodium delivery to collecting duct – Urine acidification

Question 58

what happens to the collecting duct in the presence of ADH

Answer 58

– Aquaporins become permeable to water – Passage of water from collecting tubule to interstitium down a concentration gradient – Production of concentrated urine

Question 59

what determines the concentration of the urine in the collecting duct

Answer 59

ADH

Question 60

what happens if there is a defect of ADH secretion

Answer 60

– A deficit of ADH secretion leads to copious dilute urine i.e Diabetes insipidus

Question 61

what is the renal threshold

Answer 61

* Renal threshold is the concentration of a substance dissolved in the blood above which the kidneys begin to remove it into the urine. * When the renal threshold of a substance is exceeded, reabsorption of the substance by the proximal renal tubule is incomplete and some of the substance remains in the urine.

Question 62

describe what the renal absorption of glucose is like when glucose is normal versus when it is high

Answer 62

At normal plasma glucose levels, eg 5.0 mmol/L ……… • all filtered glucose is reabsorbed • no glucose is excreted. At a plasma glucose level of about 10 mmol/L ………. • glucose appears in urine (glycosuria) • this plasma concentration is called the glucose threshold

Question 63

what is the glucose threshold

Answer 63

10 mmol/L

Question 64

why does glucose appear in the urien

Answer 64

* Glucose appears in urine because the amount of glucose exceeds the reabsorption capacity of the tubules – all the glucose carriers are saturated. * The rate of glucose reabsorption reaches a constant maximal value called the transport maximum for glucose (TmG) * The glucose threshold of about 10 mmol/L is not fixed as it depends, for example, on the GFR. * A low GFR leads to an elevated threshold - filtering rate reduced, decrease in glucose load \ more glucose reabsorbed

Question 65

how does GFR effect the renal threshold of glucose

Answer 65

* The glucose threshold of about 10 mmol/L is not fixed as it depends, for example, on the GFR. * A low GFR leads to an elevated threshold - filtering rate reduced, decrease in glucose load \ more glucose reabsorbed

Question 66

what are the side effects of glucose present in the urine

Answer 66

osmotic diuresis

Question 67

what is osmotic diuresis

Answer 67

: if excess solute present in tubular fluid this will attract water and increases urine volume (water balance lecture)

Question 68

what does increase plasma omsolaity lead to

Answer 68

Thirst sensation