Physiology of the Kidney

Question 1

How much blood enters each kidney every minute?

What % of total blood pumped by the heart is it?

Answer 1

1200ml

20%

Question 2

How is accurate measurement of glomerular filtration rate (GFR) taken?

Answer 2

Requires injection of radioactive tracer

• Technetium (Tc99)
• Chromium-51 (51Cr-EDTA)

Question 3

What is creatinine clearance used as?

Answer 3

Estimation of GFR

Question 4

Where is creatinine released from?

Answer 4

Muscle at a relatively constant rate

Relative to muscle mass

Question 5

How is creatinine then filtered?

Answer 5

Filtered by kidneys

Some secretion into the filtrate by the proximal tubule kidneys

Not that accurate for GFR (as some is secreted as well as filtered)

Question 6

As your serum creatinine levels increase, what does this indicate?

Answer 6

Loss of kidney function

Be aware of muscly people –> will have high creatinine but good kidneys

Question 7

What are problems with using serum creatinine for measuring kidney disease?

Answer 7

• Not specific for site of injury

- Delay in rise following acute kidney injury

Question 8

What tends to be used instead of creatinine clearance?

Answer 8

Estimated Glomerular Filtration Rate (eGFR)

Question 9

How is eGFR calculated?

Answer 9

• Age
• Sex
• Ethnicity
• Serum creatinine

Question 10

What does eGFR correlate with?

Answer 10

% of kidney function

e.g. eGFR = 50 = 50% kidney function

Useful when discussing with patients

Question 11

When will patients need to commence dialysis?

Answer 11

eGFR < 10mls/min/1.73m2

Question 12

What is the best treatment for kidney failure?

Answer 12

Kidney transplant

Question 13

What is dialysis?

Answer 13

Dialysis is a procedure to remove waste products and excess fluid from the blood when the kidneys stop working properly. It often involves diverting blood to a machine to be cleaned.

Question 14

What % of kidney function is lost by the time creatinine levels rise above 104μmol/L (male) i.e. normal levels?

Answer 14

50% of kidney function lost

Question 15

Where do 80% of the glomeruli lie?

Answer 15

Cortex of kidney

Question 16

What is job of proximal convoluted tubule?

Answer 16

Recovers 70% of glomerular filtrate

• Water
• Electrolytes (Na+, Cl+, K+)
• Glucose
• Amino acids
• Phosphate

Recovery and regeneration of bicarbonate

Question 17

What is the regeneration of bicarbonate dependent on?

Answer 17

Carbonic anhydrase (enzyme)

Question 18

What can a failure to recover and regenerate bicarb lead to?

Answer 18

Acidaemia (disrupts acid-base balance)

Question 19

What is taken up in the ascending limb of Henle?

Answer 19

• Na+
• K+
• 2Cl-
• H20

Sodium/Potassium/Chloride cotransporter (from lumen to inside cell)

Question 20

What drug acts at the ascending limb of Henle?

Answer 20

Loop diuretics

Question 21

How do loop diuretics work?

Answer 21

Block uptake of Na+/K+/2Cl+ cotransporter

So water is not reabsorbed and is lost in urine

Question 22

When are loop diuretics used?

Answer 22

• Cardiac failure
• Oedema
• Chronic kidney disease

Question 23

What are the side effects of diuretics?

Answer 23

• Low sodium (hyponatremia)

- Low potassium (hypokalaemia)

Question 24

What can hyponatremia lead to?

Answer 24

Serious neurological problems (coma, death)

Question 25

What can hypokalaemia lead to?

Answer 25

Cardiac arrhythmias

Question 26

What is reabsorbed at the cortical collecting duct? What is this controlled by?

Answer 26

Na+ (with H20, Cl) in exchange for K+ - Na+, Cl-, H20 out into blood - K+ into tubule Controlled by aldosterone

Question 27

What happens at the medullary collecting duct?

Answer 27

Site of urinary concentration Water, Na+ Cl-, HCO3- reabsorption

Question 28

Where does antidiuretic hormone (ADH) act?

Answer 28

Medullary collecting duct

Question 29

Where is ADH stored?

Answer 29

Posterior pituitary

Question 30

What is effect of ADH?

Answer 30

Stimulates water reabsorption --> concentrated urine

Question 31

What happens when water needs to be preserved (e.g. dehydration)?

Answer 31

ADH levels increase More water reabsorbed More concentrated urine

Question 32

What is osmolality?

Answer 32

“Osmolality” refers to the concentration of dissolved particles of chemicals and minerals -- such as sodium and other electrolytes -- in your serum. Higher osmolality means more particles in your serum. Lower osmolality means they're more diluted

Question 33

What is optimum plasma osmolality?

Answer 33

285 mOsm/L

Question 34

What is the normal daily urine output?

Answer 34

1.5-2 L of urine

Question 35

What is the normal urine osmolality?

Answer 35

50-1400 mOsm/L 50 --> very diluted 1400 --> very concentrated

Question 36

What is urine osmolality regulated to maintain?

Answer 36

Plasma osmolality

Question 37

What is it important to regulate urine osmolality?

Answer 37

To maintain plasma osmolality

Question 38

Why do the kidneys concentrate urine during periods of decreased fluid intake?

Answer 38

To conserve salt and water Maintain circulating volume and blood pressure

Question 39

What is the mechanism responsible for urine concentration called?

Answer 39

Counter current mechanism

Question 40

How does the counter current mechanism work?

Answer 40

High concentration gradient in the medulla Enables reabsorption of water from the filtrate - In proximal tubule - In collecting duct

Question 41

What is insensible loss?

Answer 41

Loss of fluid not through urine Sweating, faeces, respiration

Question 42

During states of fluid loss, what happens?

Answer 42

- Increased ADH | - Increased renin

Question 43

What is effect of increased renin?

Answer 43

Renin converts angiotensinogen to angiotensin I ACE converts angiotensin I to angiotensin II (vasoconstriction) Angiotensin II stimulates release of aldosterone which increases Na+ reabsorption

Question 44

What is glomerular filtration?

Answer 44

The movement of substances from the blood within the glomerulus into the capsular space

Question 45

What is tubular reabsorption?

Answer 45

The movement of substances from the tubular fluid back into the blood

Question 46

What is function of glomerulus?

Answer 46

Filters small solutes from blood

Question 47

What is function of Bowman's capsulse?

Answer 47

Collects what is filtered through the glomerulus

Question 48

What is the function of the proximal convoluted tubule?

Answer 48

1) Reabsorbs 65% of filtrate volume: nutrients(glucose, amino acids)/ ions(Na/bicarb)/ water 2) Secretes toxins (ammonia, creatinine, organic acids, some drugs) 3) Adjusts filtrate pH

Question 49

What is function of descending limb of loop of Henle?

Answer 49

Water reabsorption (aquaporins) = increased osmolality

Question 50

What is function of ascending limb of loop of Henle?

Answer 50

Reabsorbs Na/Cl =r educes osmolalityUrea secreted (urea recycling)

Question 51

What is function of distal convoluted tubule?

Answer 51

Hormone controlled Aldosterone: reabsorb Na (Cl follows), secrete K PTH: reabsorb Ca Reabsorb bicarb and water, synthesizes bicarb

Question 52

What is function of collecting duct?

Answer 52

Concentrates urine using osmotic gradient ADH: reabsorb water Reabsorb/secrete various ions (sodium, potassium, hydrogen ions, bicarb) to maintain blood pH

Question 53

What is GFR?

Answer 53

Refers to the ultrafiltrate of plasma which crosses the glomerular barrier into the urinary space Equal to the total filtration rates of all the functioning nephrons

Question 54

What is used instead of GFR?

Answer 54

eGFR as bette predictor of risk

Question 55

What does eGFR take into account?

Answer 55

Serum creatinine, sex, age, race

Question 56

How does ethnicity affect GFR?

Answer 56

Higher average muscle mass in African patients --> higher creatinine generation rate = higher GFR at same level of sCr

Question 57

How does sex affect GFR?

Answer 57

Men have more muscle mass

Question 58

How does age affect GFR?

Answer 58

Younger people have greater muscle mass