Renal

Question 1

What makes up the glomerular filtration barrier?

Answer 1

• Fenestrated capillary endothelium
• Glomerular basement membrane (double thickness) - negatively charged
• Podocyte foot processes (which form filtration slits- in between foot processes)

Question 2

How many percent of the cardiac output does the kidney receive?

Answer 2

20% = 1litre

Question 3

What are the functions of the kidney?

Answer 3

To maintain balance of salt, water and pH
Removal of waste products
Removal of excess fluid
Endocrine function (secreting hormones) - Erythropoietin which stimulates red blood cell production
Calcitriol - calcium and phosphate regulation
Control of blood pressure
Removal of drugs from the body

Question 4

What makes up the juxtaglomerular apparatus?

Answer 4

• Juxtaglomerular cells of the afferent glomerular arteriole
• Macula densa (of the distal convoluted tubule)

Question 5

Why is creatinine used as a marker for glomerular filtration rate? What is the gold standard marker?

Answer 5

• It is not metabolised
• Slight secretion by renal tubules (not absorbed)
• It is freely filtered

But Inulin is the gold standard - but not easy to use

Question 6

Function of mesangial cells

Answer 6

They provide structural support to the glomerular tuft.

Question 7

What are some factors affecting glomerular filtration rate?

Answer 7

• Blood pressure – increased blood pressure - increased glomerular blood flow (and hydrostatic pressure)– increased GFR
• Fluid pressure in Bowman’s space (increased hydrostatic pressure decreases glomerular filtration rate)
• Oncotic pressure in the capillary due to albumin (increased oncotic pressure decreases GFR)
• Size of molecules –> Molecules up to 10kda in size have a higher filtration rate (e.g. Glucose, amino acids, sodium and potassium, urea, creatining, HCO3-, Cl-)
• Charge of molecules –> The glomerular basement membrane has a net negative charge and thus repels negatively charged molecules
• Afferent and efferent arteriole diameter.

Question 8

Name 3 hormones the kidney produces

Answer 8

Erythropoietin
1,25 dihydroxy vitamin D3
Renin

Question 9

What is urine flow rate and what is the value of it?

Answer 9

The actual amount of urine generated by the kidney

1ml/min

Question 10

What is the order of blood vessels from the aorta to the IVC? in terms of kidneys

Answer 10

Abdominal aorta –> Renal artery –> Interlobar artery –> Arcuate artery –> Interlobular artery –> Afferent arteriole –> Glomerular capillary –> Efferent arteriole –> Peritubular capillaries –> Vasa Recta –> Interlobular vein –> Arcuate vein –> Interlobar vein –> Renal vein –> IVC

Question 11

What are the two mechanisms of intrinsic autoregulation in the kidneys?

What is their purpose?

Answer 11

• They function to maintain a constant GFR and excretion of water and waste products

1) Myogenic mechanism
2) Tubuloglomerular feedback

(Extrinsic - sympathetic stimulation, hormones)

Question 12

Explain the myogenic mechanism of instrinsic autoregulation (when bp is high) - of glomerular filtration rate

Answer 12

Higher blood pressure → exerts force and stretches the smooth muscle cells of the afferent arteriole → sodium channels open and moves into the cell making the inside of the cell more positive→ stimulating the sarcoplasmic reticulum to release calcium into the smooth muscle cell → increasing contraction of smooth muscles (vasoconstriction) → vasoconstriction of the afferent arterioles lead to a lower glomerular blood flow → lower glomerular filtration rate

Question 13

Explain the tubuloglomerular feedback

Answer 13

Higher blood pressure → higher glomerular hydrostatic pressure → higher glomerular filtration rate → more solutes and more sodium chloride are filtered into the bowman’s capsule and proximal convoluted tubule (most sodium chloride is absorbed in the proximal convoluted tubule)→ more sodium chloride makes it to the distal convoluted tubule (as channels in the PCT can’t cope) → macula densa cells detect the high levels of sodium and chloride and release adenosine→ adenosine can act on the afferent arterioles resulting in vasoconstriction (resulting in lower glomerular blood flow and lower GFR) → adenosine can also act on the juxtaglomerular cells (which contain granules of renin) to inhibit the release of renin and thus RAAS. → overall reduced the glomerular hydrostatic pressure and GFR.

(Macula densa cells release Prostaglandins and nitric oxide when blood pressure is low- triggering vasodilation of afferent arteriole AND release of renin)

Question 14

Functions of angiotensin 2 (in increasing GFR)

What is the antagonist of angiotensin 2?

Answer 14

• Angiotensin 2 stimulates the hypothalamus to stimulate the posterior pituitary to release ADH (vasopressin) → (ADH increases blood volume, increasing blood pressure, increasing GFR)
• Angiotensin 2 can stimulate your thirst centre to increase consumption of water → increasing blood volume and increasing blood pressure → increasing GFR
• Angiotensin 2 acts on the adrenal cortex (zona glomerulosa) to stimulate the release of aldosterone (mineralocorticoid) → aldosterone acts on principal cells of the collecting ducts and increases the expression of Epithelial sodium channels (ENaC) → to reabsorb sodium and water → increasing blood volume and blood pressure → increasing GFR
• Angiotensin 2 can act on the proximal convoluted tubule to increase sodium and water reabsorption → increase blood volume → increase blood pressure and GFR

Atrial natriuretic peptide is the antagonist of these functions.

Question 15

What is the normal glomerular filtration rate?
How much plasma is filtered a day?

Answer 15

125ml/min

180l of fluid passes through the kidney per day.

Question 16

What is renal clearance? What is the normal renal clearance?

Answer 16

A measure of how much of a substance can be completely removed by the kidney per unit time

A substance with a normal renal clearance of 125ml/min would indicate that the molecule is filtered and passes unchanged into the urine

A molecule with a low renal clearance e.g. 80ml/min would indicate that the molecule is filtered and reabsorbed (glucose- completely reabsorbed)

A molecule with a high renal clearance 250++ would indicate that it is filtered and actively secreted

Question 17

How does a dilation/constriction in the afferent/efferent arterioles of the kidneys affect GFR?

Answer 17

Dilate Afferent arteriole= increase GFR
Constrict Efferent arteriole= increase GFR
Due to increased blood at renal corpuscle

Constrict afferent arteriole= decrease GFR
Dilate efferent arteriole= decrease GFR
Due to decreased blood at renal corpuscle

Question 18

Definition of glomerular filtration rate
What is the formula for it?

Answer 18

A measure of the volume of fluid filtered by the glomeruli of the kidneys per unit time.

GFR= Kf (pressure in glomerular capillary - pressure in bowman’s space) - (pi x pressure in glomerular capillary)

Kf= filtration coefficient

Question 19

How does sympathetic stimulus affect GFR?

Answer 19

Increased sympathetic stimulus –> afferent arterioles constrict –> decreased renal blood flow –> decreased glomerular filtration rate

So adrenaline and noradrenaline decrease GFR

Question 20

What is filtration fraction? What is the formula?

Answer 20

The portion of plasma that is filtered across the glomerulus relative to the renal plasma flow

Filtration fraction = GFR/renal plasma flow

Question 21

Figures for renal blood flow, renal plasma flow, glomerular filtration rate and urine flow rate

Answer 21

Renal blood flow- 1250ml/min
Renal plasma flow- 700ml/min
Glomerular filtration rate- 120ml/min
Urine flow rate- 1ml/min

Question 21

Figures for renal blood flow, renal plasma flow, glomerular filtration rate and urine flow rate

Answer 21

Renal blood flow- 1250ml/min
Renal plasma flow- 700ml/min
Glomerular filtration rate- 120ml/min
Urine flow rate- 1ml/min

Question 22

Where does the bulk of reabsorption in the kidney occur?

Answer 22

Proximal convoluted tubule

Question 23

What happens in the PCT?

Answer 23

• Bulk of reabsorption in the kidneys takes place here

1) Na+ K+ ATPase - pumps 3 Na+ out and 2K+ in basolaterally

2) With the low sodium concentration in the cells, Na+ co transports glucose, amino acids, Cl- and lactate for reabsorption

3) Na+ is antiported with H+ (Na+ in, H+ out of PCT cell) (from carbonic anhydrase reaction, where CO2 enters PCT cells from the blood) - HCO3- IS REABSORBED basolaterally into the blood –> maintains electrical charge
4) Water follows sodium ions so they are reabsorbed also
5) Paracellular transport (between PCT cells) – reabsorption of Cl-, K+, Ca2+, etc

Question 24

What happens in the loop of henle?

How is hypertonicity affected as you descend and ascend the loop of henle?

Answer 24

The thick ascending limb is permeable to ions and not to water so when ions are reabsorbed, it generates a hypertonic medullary interstitium (NKCC 2 channels, Sodium and 2 chlorides are absorbed and potassium is recycled)

This hypertonic medulla causes the reabsorption of water in the thin descending limb (which is only permeable to water and not ions)

Thus the further you descend in the loop of henle, the higher the osmolality. The further you ascend, the more lower the osmolality (low osmolality=hypotonic)

Question 25

Function of the vasa recta

Answer 25

They contain hairpin loops which run parallel to the loop of henle. They run in opposite directions to the loops of henle.

• They supply oxygen and nutrients to the renal medulla
• It has a counter current exchange mechanism which allows the maintenance of the concentration gradient in the renal medulla
• It reabsorbs water and solutes back into the blood stream.

Question 26

What happens in the DCT?

Answer 26

• Sodium and chloride reabsorption via sodium chloride symporter
• PTH can promote calcium reabsorption (via cyclic AMP, protein kinase –> calcium channels)
• Aldosterone can increase sodium reabsorption and potassium excretion
• ADH can upregulate aquaporins, increasing water reabsorption.

Question 27

What happens in the collecting duct?

Answer 27

Intercalated cells
- Are involved in secreting H+ in exchange for K+ (the HCO3- is reabsorbed from the carbonic anhydrase reaction)

Principal cells
- ADH upregulates aquaporin channels which increases water reabsorption

• Aldosterone acts on ENaC channels which reabsorbs sodium and excretes potassium

Question 28

Where is ADH made and secreted?

Answer 28

ADH is made by the hypothalamus but released by the posterior pituitary.

Question 29

What kind of hormone is aldosterone?

Answer 29

Steroid hormone- made from lipid cholesterol

Question 30

What are the functions of aldosterone?

Answer 30

• Acts on the distal convoluted tubules and collecting ducts to increase sodium reabsorption (and thus water reabsorption) and potassium excretion
  THIS NOT ONLY HELPS WITH BLOOD PRESSURE CONTROL BUT ALSO ELECTROLYTE BALANCING

Question 31

What is the difference between acidosis and acidemia? Alkalosis and alkalemia also

Answer 31

Acidosis is a disorder tending to make blood more acidic than normal

Acidemia means low blood pH (pH <7.35)

Alkalosis is a disorder tending to make blood more alkaline than normal

Alkalemia means high blood pH (pH > 7.45

Question 32

What nerves innervate the bladder? Are they parasympathetic or sympathetic?
What muscles does it have?

Answer 32

Pelvic splanchnic nerves (S2-S4)

Parasympathetic nerves

It has detrusor muscles

Question 33

What nerves innervate the internal urethral sphincter? Are they parasympathetic or sympathetic?
What muscles does it have?

Answer 33

Innervated by sympathetic fibres from the hypogastric nerve T10 - L2

It has smooth muscle

Question 34

What nerves innervate the external urethral sphincter? Are they parasympathetic or sympathetic?
What muscles does it have?

Answer 34

Innervated by somatic pudendal nerve S2-S4

It has skeletal muscle

Question 35

What is happening with the sympathetic and somatic motor neurones when the bladder is empty?

Answer 35

• Sympathetic motor neurone are stimulated to cause the detrusor muscle of the bladder to relax and the internal urethral sphincter to constrict for STORAGE OF URINE.
• Somatic motor neurones keep the external urethral sphincter constricted

Question 36

What is the bladder stretch reflex?

Answer 36

As the bladder fills, stretch of the bladder wall is detected and this is relayed to the sacral spinal cord via visceral afferent fibres. In the sacral spinal cord, they synapse directly onto motor neurons which via parasympathetic fibres of the pelvic splanchnic nerves, cause bladder contraction and relaxation of the internal urethral sphincter.
Referred to as the reflex arc

After ‘potty training’ this reflex arc can be inhibited by inputs from the cerebral cortex (in older children and adults)– we learn to consciously recognise bladder filling and develop descending pathways that inhibit the reflex when it is not convenient to urinate.

Question 37

What bladder dysfunction happens when a patient suffers an injury to their spinal cord above the sacral level (at the level of T10)?

Answer 37

2 pathways are interrupted
Ascending pathways conveying the sensation of bladder filling to the brain (patient no longer aware of bladder filling) are interrupted
Descending pathways that exert voluntary, inhibitory control over the external urethral sphincter (so external sphincter is permanently relaxed) are interrupted
So the reflex arc still functions below the injury but the patient no longer has control over it. (the patient does not realise they need to pass urine and the bladder automatically empties as it fills - the patient is incontinent of urine)- urinary incontinence

Question 38

What bladder dysfunction happens when a patient suffers an injury to the spinal cord or cauda equina at or below the level of sacral micturition centres?

Answer 38

The reflex arc is disrupted and the bladder fills with urine without emptying. The internal urethral sphincter is permanently contracted

So as the bladder continues to fill, the pressure in the bladder eventually exceeds the strength of the internal urethral sphincter and urination will occur. Referred to as overflow incontinence

However if the pressure in the bladder does not overcome the strength of the internal sphincter, the patient develops urinary retention→ eventually urine may back up to the ureters and kidneys if a urinary catheter is not placed.

Question 39

What level is the sacral micturition centres?

Answer 39

S2-S4

Question 40

What are the effects of somatic, parasympathetic and sympathetic innervation on the bladder. Where do they arise from?

Answer 40

Somatic- Via branches of the pudendal nerve (S2-S4) → this allows for conscious control of the external urethral sphincter

Sympathetic- Via branches of the hypogastric nerve (T12-L2- sympathetic chain) → it causes relaxation of the detrusor and contraction of the internal urethral sphincter, allowing storage of urine.
Parasympathetic- Via the pelvic splanchnic nerves (S2-S4) → It causes contraction of the detrusor and relaxation of the internal urethral sphincter, allowing initiation of micturition