Renal physiology

Question 1

What is the juxtaglomerular complex and what is its function?

Answer 1

Anatomically close to the corresponding glomerulus, contains cells that regulate renal blood flow.

Granular cells - renin secretion (afferent arteriolar wall)
Macula densa - senses tubular Na and Cl concentrations
Extra glomerular mesangial cells - interacts with macula densa to control granular cells, and smooth muscle of afferent arteriole

Question 2

How much blood flow do the kidneys receive?

Answer 2

20% of cardiac output, 1000mL/ min (500 to glomerulus)

Question 3

What range is renal perfusion pressures autoregulated to stay in adequate range?

Answer 3

MAP 75-165

Question 4

What mechanism in auto regulation increases and decreases GFR?

Answer 4

Constricting efferent arteriole increases capillary hydrostatic pressure therefore increasing GFR.

Constricting afferent arteriole decreases capillary hydrostatic pressure therefore decreasing GFR.

Question 5

How does angiotensin 2 increase renal perfusion pressure?

Answer 5

1. Kidneys- constricts afferent and efferent arteriole, efferent more so increases systemic blood pressure but preserves GFR.
2. Vaso and veno vasoconstriction - increase systemic BP
3. Adrenal gland - aldosterone release which acts on DCT and CD to reabsorb Na and Water - expand plasma volume
4. Brain
   - hypothalamus (increases thirst + ADH release which increases Water reabsorbtion CD)
   - noradrenaline release (vasoconstrictor)

Question 6

Glomerulonephritis sites and disease caused:
A. Basement membrane, 
B. podocytes, 
C. mesangial cells, 
D. Glomerular capillaries

Answer 6

A. Good pastures
B. Minimal change disease
C. Immunoglobulin A nephropathy - IgA deposits
D. SLE, RA - antigen antibody complex deposition

Question 7

What substance is used to measure renal blood flow?

Answer 7

PAH: para-amino hippuric acid

used to calculate renal plasma flow as filtered amount is equals to plasma conc in afferent vessels. Then using haematocrit can calculate RBF

Question 8

What size and charge particles can be filtered in glomerular capillaries?

Answer 8

7 kDa freely filter into Bowmans capsule.
7-70 kDa partially filter.
Positive charge are filtered.
Small anions are filtered, but larger negatively charged proteins are repelled.
Basement membrane and podocyte foot process are negative.

Question 9

What substances are passively and actively absorbed?

Answer 9

Water is passively reabsorbed alongside some dissolved electrolytes and small molecules like urea.

Most other substances are active.

Question 10

Where does most reabsorbtion occur?

Answer 10

PCT

Question 11

Define renal clearance.

Answer 11

The clearance of a substance (mL/ min) is

the volume of plasma completely cleared
of that substance by the kidneys
per unit time.

Question 12

What is the typical GFR in a healthy human?

Answer 12

125mL/ min. 180 L per day.

Question 13

What’s is the typical osmotic hydrostatic pressure inside and outside the glomerular capillary?

Oncotic pressures?

Answer 13

Inside - 48 mmHg
Outside - 10 mmHg
Therefore across the membrane a driving hydrostatic pressure of 38mmHg

Oncotic- same as osmotic pressures of plasma proteins = 25 mmHg

Question 14

What is the gold standard in measurement of clearance?

Answer 14

Measurement using INULIN,

an exogenous polysaccharide which needs to be infused for measure of output.

Question 15

Why is creatinine clearance not an accurate measure of GFR?

Answer 15

Creatinine production varies between individuals as it is dependent on skeletal muscle mass and affected by age, sex, race etc. Also 10-20% actively secreted, not filtered. Therefore overestimates GFR.

By measuring plasma creatinine alone you could have no change with a 50% drop in GFR.

Question 16

What fraction of body water is intracellular and extracellular?

Answer 16

2/3 intracellular

1/3 extracellular

Question 17

What fraction of extra cellular fluid is intravascular?

Answer 17

1/5 - 3L in a 70kg man

Question 18

What is osmolarity?

Answer 18

A measure of the number of dissolved osmotically active particles per unit volume of a solution.

• the number of osmoles per litre solution

Question 19

What is osmolality?

How is it different from osmolarity?

Answer 19

Osmolality is the measure of the number of osmotically active particles per unit MASS of a solution. (The number for is osmoles per kg of solvent)

Based upon mass instead because osmolarity is affected by changes in volume and temperature whereas mass is not.

Question 20

Osmolar gap equation

What is the significance of an osmolar gap, and what conditions can it be seen in?

Answer 20

(Na + K) - (glucose + urea)

Osmolar gap = Osmolality (measured) – Osmolarity (calculated)

normal = < 10

if elevated consider presence of other osmotically active particles

mannitol
methanol
ethylene glycol
sorbitol
polyethylene glycol (IV lorazepam)
propylene glycol (IV lorazepam, diazepam and phenytoin)
glycine (TURP syndrome)
maltose (IV IG – Intragram)

Question 21

What is the normal plasma osmolarity?

Answer 21

285-295 mOsmol/L

Question 22

How is plasma osmolarity controlled ie increasing?

Answer 22

1. Osmoreceptors in the organum vasulosum, laminators terminalis - hypothalamus detect even a 1% change
2. Effector - hypothalamus stimulates thirst, ADH secretion; increasing body water

Question 23

How does ADH affect the kidney? [mechanism]

Answer 23

Acts on the collecting ducts which are usually impermeable to water.

Binds to V2 receptors, through a cyclic AMP system resulting in a water channel [aquaporin 2] being inserted into the collecting luminal wall.

Water flows along osmotic gradient, rental medulla has a very high osmolarity generated by the loops of henle.

Question 24

What is the function of the different parts of the loops of henle?

Answer 24

1. Thin descending limb - permeable to water only
2. Thin ascending limb - permeable to ions only
3. Thick ascending limb - permeable to ions only but also moves ions via secondary active transport via co-transporters

Question 25

What alterations to filtrate occur at the PCT?

Answer 25

PCT is permeable to water, glucose, amino acids and ions which are all reabsorbed.

Therefore by the end when it reaches the descending limb of the LOH it should have roughly the same osmolality as plasma - 300 mOsmol/L

Question 26

Which part of LOH has the highest osmolarity and why?

Answer 26

Tip of LOH.
1200 mOsmol/L
Because the water has been moved out in the descending limb, and all the ions are still present prior to entering the ascending limb for transport.

Question 27

How does the vasa recta prevent washout of the osmotic gradient?

Answer 27

It anatomically follows the loop of henle in a hairpin loop arrangement with flow in the opposite direction and equilibrates with the surrounding interstitium, therefore by the time it reaches the PCT is should have an osmolarity similar to plasma 320.

Question 28

How is central diabetes insipidus a disorder of osmolarity?

Answer 28

Damage to the posterior lobe of the pituitary gland results in failure to secrete adequate ADH. Water cannot be reabsorbed at the collecting ducts = excessive urination + hypovolaemia.

This leads to hypernatraemia, high plasma osmolarity and and inappropriate low urine osmolarity.

Question 29

SIADH: how does this affect osmolarity?

Answer 29

Excess ADH secretion from post pituitary lobe or ectopic source like small cell lung ca.

Excess water reabsorbtion.

Features of hyponatraemia- headache, nausea, confusion, seizures, coma.

Low plasma osmolarity, high urine osmolarity.

Question 30

How does the kidney regulate Na excretion?

Answer 30

1. Changes in GFR depending on plasma volume
2. Changes in reabsorbtion
   - bulk reabsorbtion: 60% PCT, 30% LOH
   - DCT and collection ducts do the rest via aldosterone

Question 31

What are the hypovolaemia hormones?

Answer 31

Noradrenaline - reduce GFR and Na excretion

Renin - angiotensin 2( Na reabsorb at PCT + reduce GFR) and aldosterone (reduce Na secretion at DCT)

ADH - water reabsorb

Question 32

Where do the loop diuretics act?

Answer 32

At the thick ascending limb on inhibition of the Na/K/Cl co transporter so they are no reabsorbed, and disrupts the medullary osmotic gradient.

Question 33

Where do thiazides diuretics act?

Answer 33

At the DCT blocking Na/ Cl co transporters.

Question 34

Where do potassium soaring diuretics act?

Answer 34

At the DCT and collecting duct blocking the aldosterone receptors therefore increasing Na excretion and reducing H+ and K excretion.

Question 35

What mechanisms trigger the movement of potassium intra and extracellular?

Answer 35

1. Insulin - INTO CELLS: increases activity of Na/ K ATPase, increasing intracellular uptake
2. Sympathetic stimulation:
   - a-adrenrenoreceptors: K+ release from the cells, during exercise important for muscles to have a local hyperkalaemia to stimulate glucogenolysis + vasodilation

• B2-adrenorecptors: K+ uptake.

Question 36

How is plasma K+ regulated by the kidneys?

Answer 36

Freely filtered at the glomerulus,
Majority reabsorbed at PCT and LOH.
Regulation occurs at DCT and CD where it can be excreted whilst Na is reabsorbed via aldosterone.