Physiology

Question 1

Name the 6 main functions of the urinary system (kidney)

Answer 1

1. maintain water and salt balance
2. maintain blood pH
3. excretion of metabolic waste products
4. blood glucose regulation (glucose reuptake and gluconeogenesis during fasting period)
5. endocrone functions - production of renin and EPO
6. production of vitamin D

Question 2

1. name the two basic components of the nephron
2. what is the location of cortical nephrons?
3. what is the location of juxtamedullary nephrons?

Answer 2

1. renal corpuscle - glomerular capillaries and bowman’s capsule
   renal tubule - PCT, LoH, DCT, CD
2. lie in the outer portion of the renal cortex; short nephron loops that penetrate only into the outer region of the renal medulla
3. lie deep in the cortex; long nephron loops extend deep into the medulla

Question 3

Describe the histology of the following structures:

1. Bowman’s capsule
2. PCT
3. Loop of Henle
4. DCT
5. describe the two capillary beds in the nephron

Answer 3

1. visceral layer consists of podocytes; parietal layer consists of simple squamous epithelium
2. simple cuboidal
3. simple squamous
4. simple cuboidal - principal cells and intercalated cells
5. glomerular capillaries - specialised for filtration; surrounded by pedicels of podocytes. fed by afferent arterioles; drained by efferent arterioles
   peritubular capillaries/vasa recta; lie close to the renal tubule; specialised for absorption. Fed by efferent arterioles; drained by venules

Question 4

1. what is the filtration fraction?
2. what is the normal filtration volume?
3. what is GFR?
4. what is the normal GFR?

Answer 4

1. fraction of blood plasma in the afferent arterioles that becomes the glomerular filtrate
2. 180L per day
3. the volume of plasma that is filtered into Bowman’s space per unit time
4. 125ml/min

Question 5

describe the three layers of the filtration membrane, and what they permit/prevent

Answer 5

1. glomerular endothelial cells
   - large fenestrations make them leaky
   - permits all solutes; prevents blood cells and platelets
2. basement membrane
   - collagen fibres and proteoglycans
   - negative charges prevents filtration of large, negatively charged plasma proteins
3. slit membrane between pedicels
   - permits passage of small molecules - glucose, water, vitamins, amino acids, v. small plasma proteins, ammonia, urea, ions

Question 6

describe the 3 filtration pressures governing glomerular filtration

Answer 6

1. glomerular blood hydrostatic pressure - BP in glomerular capillaries
2. Capsular hydrostatic pressure - pressure exerted against the filtration membrane by fluid in capsular space (opposes filtration)
3. Blood colloid osmotic pressure - osmotic pressure exerted by blood plasma proteins (opposes filtration)

Question 7

1. what is autoregulation?
2. why is autoregulation important?
3. describe the myogenic mechanism driving autoregulation
4. describe tubuloglomerulofeedback

Answer 7

1. local adjustment of blood glow to the kidneys based on their immediate requirements
2. if GFR is too high, needed substances pass too quickly through the tubules and are not absorbed. If GFR is too low, nearly all the filtrate will be reabsorbed
3. as BP rises, afferent arteroles are stretched. This triggers contraction of smooth muscle cells in afferent arterole wall
4. macula densa cells in TAL respond to filtrate [NaCl]. Increases in GFR cayses filtrate [NaCl] to rise > macula densa cells release vasoconstrictive chemicals > reduction in glomerular blood flow.
   Macula densa cells also signal to the Juxtaglomerular apparatus to release renin.

Question 8

1. describe the RAAS cascade

2. describe the effects of angiotensin II

Answer 8

1. enin converts angiotensinogen to angiotensin I. ACE converts angiotensin I to angiotensin II.
2. stimulate Na/H antiporters > sodium retention
   increase sympathetic activity > vasoconstriction
   production of aldosterone > stimulation of Na/K ATPase and ENaC
   production of ADH > water retention

Question 9

1. what is renal clearance
2. what equation is used to calculate renal clearance
3. which substance is ideally used to measure clearance and why?
4. which substance is clinically used to measure clearance and why?
5. what is clearance used to calculate?

Answer 9

1. the volume of plasma that is cleared of a substance in one minute
2. C=(UxV)/P
   U = urinary concentration of substance
   V = urine flow rate (ml/min)
   P = plasma concentration of substance
3. inulin, as it is a substance that is neither secreted or reabsorbed
4. creatinine. freely filtered, but secreted in small amounts. does not need to be intravenously infused
5. GFR

Question 10

which side of the membrane faces the:

1. tubular fluid
2. interstitial fluid

Answer 10

1. apical membrane

2. basolateral membrane

Question 11

Describe the main reabsorption/secretion events occuring in the following:

1. PCT
2. descending limb
3. ascending limb
4. DCT
5. collecting duct

Answer 11

1. reabsorption of majority of substances - mostly coupled to sodium.
   H+ secretion
2. water reabsorption (expression of AQP1)
3. secondary active transport of Na/K/Cl
   passive paracellular absorption of Ca and Mg
4. secondary active transport of NaCl
   passive absorption of Ca via PTH regulated TRPV5 channels
5. Na, K and bicarbonate reabsorption
   regulated K+ secretion
   H+ secretion
   regulated water and urea reabsorption

Question 12

name the main transporters involved in sodium reabsorption in:

1. proximal tubule
2. loop of henle
3. early distal convoluted tubule
4. late distal tubule and collecting duct

Answer 12

1. various co-transporters
   NHE3 couples sodium reabsorption to H+ secretion
2. NKCC2
3. NCC
4. ENaC

Question 13

describe the effects of the following hormones:

1. angiotensin II
2. Aldosterone
3. ADH
4. PTH

Answer 13

1. stimulates Na/H Antiporters
2. stimulates Na/K ATPase and ENaC
3. stiumulates insertion of AQP2 and urea transporters in the principal cells
4. stimulates opening of TRPV5 channels in DCT

Question 14

POTASSIUM HANDLING

1. describe potassium handling in
   a) proximal tubule
   b) loop of henle
2. what is the role of alpha intercalated cells? what transport proteins facilitate this?
3. what is the role of principal cells? what transport proteins facilitate this?

Answer 14

1a) paracellular reabsorption - K is dragged along with water
1b) paracellular reabsorption and transcellular via NKCC2 and a BL potassium channel
2. K+ reabsorption - driven by K+/H+ ATPase and basolateral K+ channel
3. Potassium secretion - driven by basolateral Na/K ATPase and apical K+ channel and K+/Cl- cotransporter

Question 15

1. what is a xenbiotic?
2. define anuria
3. define polyuria

Answer 15

1. a substance that is foreign to a given biological system
2. no urine
3. too much urine

Question 16

1. what type of diet is more:
   a) alkaline
   b) acidic
2. how does urine pH affect clearance of substances?
   a) acidic urine
   b) basic urine?
3. Why is this?
4. What does this have implications for?

Answer 16

1a) fruit/vegetable based
b) protein based

2a) increased clearance of basic drugs
b) increased clearance of acidic drugs
3. affects drug ionisation (unionised at same pH) and therefore stay in the blood - cleared at a slower rate
4. has implications for T1/2 and drug dosing, and drug toxicity

Question 17

Describe the MOA and give examples of the following drugs:

1. D-mannitol
2. carbonic anhydrase inhibitors
3. loop diuretics
4. thiazide diuretics
5. amiloride
6. spironolactone
7. why do loop diuretics and thiazide diuretics cause hypokalaemia?

Answer 17

1. increases the osmotic pressure of the tubular fluid therefore more water is kept in the filtrate
2. prevents the exchange of Na for H+ - sodium stays in the tubular fluid and water stays with it. e.g. acetazolomide
3. inhibits NKCC2 in tAL
4. inhibits NCC in the DCT
5. Inhibits ENaC in the collecting duct
6. aldosterone antagonist
7. Increase sodium delivery to the distal tubule - this stimulates the aldosterone-sensitive sodium/potassium pump to increase sodium reabsorption in exchange for potassium and hydrogen ion, which are lost to the urine

Question 18

why can treating cancer co-morbidities difficult?

Answer 18

because common chemotherapy drugs have significant renal toxicity

Question 19

1. where does the net intake of acids come from?
2. describe the 3 systems that regulate blood pH
3. how are volatile acid loads handled?
4. how are non volatile acid loads handled?

Answer 19

1. diet and metabolism
2. buffer systems
   respiratory system
   renal system
3. handled by the lungs (volatile acid load is mainly CO2)
4. kidneys

Question 20

draw equations for the following buffers

1. phosphate
2. ammonia
3. proteins
4. bicarbonate
5. which of the above are
   a) renal buffers
   b) plasma buffers
   c) intracellular buffers
   d) extracellular buffers

Answer 20

1. HPO4- + H+ ⇌ H2PO4
2. NH3 + H+ ⇌ NH4+
3. Hb + H+ ⇌ HHb
4. H2O + CO2 ⇌ H2CO3 ⇌ H+ + HCO3-

5a) phosphate, ammonia and bicarbonate
5b) phosphate and protein
5c) proteins
5d) bicarbonate

Question 21

1. what are the two roles of the kidney in acid base balance?
2. describe the process of bicarbonate reabsorption
3. what facilitates movement of bicarbonate across the basolateral membrane?
4. what facilitates the movement of H+ across the apical membrane?

Answer 21

1. maintain the concentrations of bicarbonate in the body & regenerate bicarbonate from CO2 when CO2 is in excess
   secretion of non volatile acid load
2. H+ is secreted into the lumen by NHE. This titrates with filtered HCO3-
   carbonic anhydrase catalyses the production of H2O and CO2
   CO2 and H2O diffuse into the cell
   inside the cell, CO2 and H2O become H+ and HCO3-
   H+ is recycled; HCO3 crosses the basolateral membrane
3. bicarbonate-chloride exchanger
   sodium-bicarbonate co-transporter
4. Na/H exchanger
   H+ pump - found in alpha intercalated cells
   H/K exchanger - found in collecting duct cells

Question 22

1. why does the urine need to have buffer systems?

2. how does the kidney make ammonia?

Answer 22

1. to ensure that urine pH does not become too low

2. from the breakdown of glutamine

Question 23

1. what causes the following:
   a) respiratory acidosis
   b) respiratory alkalosis
   c) metabolic acidosis
   d) metabolic alkalosis
2. describe respiratory mechanisms to:
   a) acidosis
   b) alkalosis
3. describe renal mechanisms to
   a) acidosis
   b) alkalosis

Answer 23

1a) decreased ventilation
1b) hyperventilation
1c) generation of ketone bodies (diabetes), diarrhoea
1d) vomiting, ingestion of excess bicarbonate

2a) increased ventilation
2b) decreased ventilation

3a) secretion of more acid; production of new bicarbonate
3b) reduced reabsorption of bicarbonate & secretion of bicarbonate

Question 24

In terms of acid base balance, what is the role of

1. alpha intercalated cells
2. beta intercalated cells

What is the apical and basolateral arrangements of transporters in these cells

Answer 24

1. secrete acid and absorb bicarbonate
2. absorb acid and secrete bicarbonate
3. alpha cells - apical K/H co-transporter & H+ ATPase; basolateral Cl/HCO3- exchangers
   beta cells; apical Cl/HCO3- exchangers; basolateral K/H co-transporter & H+ ATPase

Question 25

EXAMINATION OF ARTERIAL BLOOD GASSES

1. how do you tell if a patient is alkalotic or acidotic?
2. how do you examine what the primary problem is?
3. How can you tell if the patient is compensating?

Answer 25

1. examine blood pH
2. examine CO2 and bicarbonate levels
   (CO2 abnormal if resp; bicarbonate abnormal if renal)
3. examine PCO2 and bicarbonate levels in respect to pH
   - if PCO2 and bicarb are high, and pH is low - resp acidosis with renal compensation
   - if PCO2 and bicarb are high with high pH - metabolic alkalosis with resp compensation

Question 26

1. Name 4 reasons why infants are more susceptible to acid base imbalance
2. name 2 reasons why the elderly are more prone to acid base imbalance

Answer 26

1. low lung voliume
   excessive fluid shift
   high metabolic rate
   inefficiency of kidneys
2. decrease in total body volume
   unresponsive to thirst cues