Renal Systems

Question 1

Urine drainage in the kidney

Answer 1

Collecting duct-> Papillary duct->minor calices-> major calices-> Renal pelvis-> Ureter

Question 2

Order of renal vasculature

Answer 2

Renal artery –> Interlobar artery–> Arcuate artery –> Interlobular artery –> Afferent glomerular arteriole –> Glomerulus–> Efferent glomerular arteriole–>

a) descending vasa recta–>medullary peritubular arteries–>ascending vasa recta–> interlobular veins–> arcuate veins–>interlobar veins–>renal vein.
b) cortical peritubular capillaries–> interlobular veins–> arcuate veins–> interlobar veins–> renal veins.

Question 3

Structure of Bowman’s Capsule

Answer 3

Simple squamous epithelium on the parietal side- capsular/parietal epithelium.
Visceral epithelium is made of podocytes.

Question 4

Structure of the glomerular filter.

Answer 4

Fenestrated endothelium: Innermost layer- capillary wall. Has many large holes and only retains large blood proteins and blood cells.
Basement lamina- Combined basement membrane secreted by the podocytes and the endothelium.
Podocytes: Epithelial cells with a raised nucleus and many pedicels/projections, which interlock to form filtration slits., which are covered by slit membranes.

Question 5

Effect and symptom of damage to the filter

Answer 5

Damage to the filters will allow larger molecules to move out. This can be indicated by foaming of urine, brought about by the presence of proteins

Question 6

Volume and distribution of fluid in the body

Input and output of fluid

Answer 6

60% in males and 55% in females.
2/3 of all fluid found as cytosol and rest is extracellular fluid.
80% of extracellular fluid is interstitial fluid, while 20% is blood plasma.
INPUT: 64% beverages, 28% food, 8% from reduction of oxygen at ETC.
OUTPUT: 60% urine, but highly regulated according to homeostasis. 24% sweat, 12% lungs (moisturising air), 4% faeces.

Question 7

Relative ion concentrations

Answer 7

Na+: ~150mM extracellular, 10mM intracellular
K+: 5mM extracellular, 140mM intracellular
Cl-:4mM extracellular, 110mM intracellular

Question 8

Renal perfusion figures

Answer 8

125mL/min. 180L daily. 25% per cardiac cycle. 178.5L reabsorbed. ALL GLUCOSE REABSORBED

Question 9

Pressures affecting Renal Perfusion

Answer 9

NFP: Net filtration pressure.
GBHP: Glomerular blood hydrostatic pressure. Force driving filtration due to high arteriolar blood pressure.
BCOP: Blood colloidal osmotic pressure. Force driving reabsorption due to the proteins in blood reducing osmolarity.
CHP: Capsular hydrostatic pressure. Force driving reabsorption due to the recoil force of the capsule forcing fluids back.
NFP=BGHP-CHP-BCOP

Question 10

Variation of glomerular filtration//urine production with MAP variation `

Answer 10

Below the normal range of MAP, increase in MAP causes a steep increase in renal blood flow and hence filtration. (filtration rate slightly lower as not all blood is filtered out)
At physiological MAP, the renal blood flow and filtration is approximately constant, to allow for biological fluctuations.
Urine production follows a roughly linear increase with MAP, even at around 100mmHg. Due to other factors besides glomerular perfusion affecting urine formation (ie: affects reabsorption).

Question 11

Tuboglomerular Feedback

Answer 11

Ascending limb of Loop of Henle is found near the afferent and efferent arterioles and has macula densa cells in its walls. Monitors [Na+] and [Cl-] in the blood and in the case of excess [Na+] , NO release by the JG apparatus is inhibited and contraction of smooth muscle occurs.
Excess [Na+] is due to GFR being too high, so there isn’t enough time for Na+ to be reabsorbed from the filtrate. By reducing MAP, filtration is less favoured, so filtrate moves through at a lower rate and more time is given for the reabsorption of Na+.

Question 12

Myogenic Regulation Mechanism

Answer 12

As blood volumes increases, it is detected by smooth muscles in blood vessel walls as increased blood pressure. This causes the smooth muscle to stretch, which increases its ability to contract and hence can vasoconstrict more strongly.

Question 13

Neural and Hormonal Regulation of Renal Smooth Muscle

Answer 13

Sympathetic innervation activates the smooth muscle by causing epinephrine to bind to alpha-1 receptors.
Angiotensin II has a similar effect that results in vasoconstriction.
ANP (Atrial natriuesis peptide) stimulates the relaxation of mesangial cells found in between glomerular capillaries, increasing the SA of the capillaries.

Question 14

Reabsorption at the Proximal Convoluted Tubule.

Answer 14

Most reabsorption occurs in the PCT (60% NaCl and H2O. ALL glucose).
Brush border present due to nonciliated epithelium- maximises surface area. Epithelial cells here are large and have many mitochondria to produce enough ATP to power the NaKATPase.
Na+ is reabsorbed by diffusion. Glucose is reabsorbed by Na cotransporter. In diabetics, this transporter is saturated, so glucose is present in the urine.
Water is reabsorbed via paracellular reabsorption as it moves down the osmolarity gradient and into the basal interstitial space. Another pathway is through aquaporin-1s on the walls of the epithelium.

Question 15

Reabsorption in the Loop of Henle (Not the countercurrent stuff)

Answer 15

Descending: No ion channels so only permeable to water. Water moves out into the lower osmolarity medulla- osmolarity increases medially. As more water is drawn out, filtrate becomes more concentrated and the medulla must also become more ‘salty’ to maintain the osmotic gradient- filtrate is 1200mOsmol at the bottom of the loop.
Ascending: Walls impermeable to water due to absence of aquaporins. Epithelial cells here are very metabolically active to allow for activation of NaKATPase. Na+ diffuses from lumen into the epithelial cells via the NaK2Cl cotransporter, which transports K+ and 2Cl-s into the cell as well. As the filtrate ascends, it becomes more dilute, so the medulla maintains the gradient by rapidly removing the ions via vasculature.

Question 16

Countercurrent Multiplication

Answer 16

CREATES and INCREASES the osmotic gradient used during reabsorption.
Diffusion of Na+ and Cl- ions into the medulla increases its osmolarity, so the osmotic gradient is steeper and more water is able to be reabsorbed.

Question 17

Countercurrent Exchange

Answer 17

MAINTENANCE of the osmotic gradient used in reaborption.
The vasa recta moves in the opposite direction to the direction of filtrate movement. At the descending vasa recta, the interstitial fluid is hyperosmotic relative to the blood plasma, because of all the ions which diffuse out, so ions enter the vasa recta, while water diffuses out, which dilutes the interstitial fluid.
At the ascending vasa recta, the movement of water out from the descending limb will dilute the interstitial fluid around it. The hypo-osmotic environment drives diffusion of ions (which entered the VR from the ascending limb of the LoH) from the vasa recta, while water enters by osmosis.

Question 18

Reabsorption at the DCT and Collecting Duct

Answer 18

The DCT epithelial cells express NaKATPase to reabsorb more Na+. In isolation, there are no aquaporin-2s on the epithelium, but since ADH is constantly secreted at a baseline level, there is some permeability to water.

Question 19

Secretion and Function: ADH/Arginine Vasopressin

Answer 19

Neurosecretory hormone produced at the hypothalamus and transported for storage and secretion at the posterior pituitary.
Effects include increasing expression of aquaporin-2s in the epithelium of the DCT and collecting duct.
Secondary effect of causing vasoconstriction.

Question 20

Relationship between ADH release and blood osmolarity at different blood volumes.

Answer 20

The blood osmolarity threshold for ADH release is 280mOsmols (slightly below physiological blood osmolarity), while for the thirst response it’s 295mOsmol- less exquisite regulation.
The response to osmolarity change is stronger in hypovolemia, as the volume is already low, so as osmolarity increases, ADH release also increases to prevent water loss from further increasing osmolarity.

Question 21

Mechanism of controlling ADH release

Answer 21

Blood osmolarity detected by paraventricular nuclei- cells with stretch inhibited Na+ channels.
If blood osmolarity is low, water leaves the cell and it shrinks. Since the cell is tethered at points on the membrane, as the membrane shrinks the channels will be pulled open. This allows Na+ influx, which stimulates vesicle exocytosis.
Similarly, baroreceptors in atria and large vessels can detect LARGE reductions in blood pressure caused by reduced blood volume. This stimulates the posterior hypothalamus via sympathetic nerves. This is less exquisite than the osmoreceptors, as small changes in pressure is usually can be fixed by baroflex.

Question 22

Mechanism of Renin Release

Answer 22

NaCl concentration is detected at the distal convoluted tubule by the macula densa cells. Reduced NaCl content will result in increased prostaglandin release, which triggers JG apparatus to release renin.
Note: It detects NaCl content, which is MORE than NaCl conc. This can be caused by reduced blood volume as well.
Hence, other effects of reduced blood volume, such as the bareoflex, can trigger this via sympathetic innervation OR reduction of pressure detected by baroreceptors in the afferent arterioles.

Question 23

Mechanism of Angiotensin II release and Angiotensin II properties.

Answer 23

Renin cleaves the readily available angiotensinogen in the liver, forming angiotensin I. Angiotensin I then is converted to angiotensin II by angiotensin converting enzyme, which is produced by the lung.
Angiotensin II stimulates vasoconstriction, which increases blood pressure and reduces renal perfusion to reduce GFR.

Question 24

Mechanism of Aldosterone Release

Answer 24

Aldosterone is released by the zona glomerulosa of the cortex, which releases mineralocorticoids. Travels to the DCT and upregulates the expression of NaKATPase on epithelium. This upregulates Na+ reabsorption (and K+ secretion into the lumen but that’s not important), meaning the osmolarity gradient is directed out of the lumen, and water also moves out via osmosis.
(The last bit requires cooperation with ADH to upregulate expression of aquaporin-2s. )

Question 25

Mechanism of ANP release, and its function

Answer 25

Increasing blood volume stretches the atria and stimulates the release of ANP. (Increasing blood volume means increased NaCl content).
ANP secretion is coupled with inhibition of ADH, aldosterons, and renin, as well as stimulation of afferent glomerular arteriole dilation.
This increases GFR while also reducing proteins needed for water and Na+ reabsorption

Question 26

What’s special about volumetric loss and gain of blood?

Answer 26

They should be iso-osmotic changes (unless stated otherwise). This means both RAA and ADH would be activated, enabling excretion of both solutes and water.

Question 27

Timing of Regulatory Responses to Blood Volume Change

Answer 27

Autoregulatory/ANS Response: VERY quick (seconds) and useful against biological fluctuations. Protects vessels against sudden surges.
Hormonal Response: Only activated after prolonged changes in pressure due to changes in volume. This prevents sudden pressure fluctuations at normal volume to cause an enzyme cascade- wastes resources and has no real effect.

Question 28

Mechanism for inducing thirst.

Answer 28

Hormones secreted during the volume change response will also stimulate a thirst response at the hypothalamus. Reduction in saliva production causes a dry mouth, which is registered by the somatosensory pathway as thirst.