Renal- Overview of kidney function

Question 1

What is the need for kidney function

Answer 1

Maintain homeostasis and excrete nitrogenous waste (e.g. urea, creatinine).
 Electrolytes or nutrients are absorbed in the proximal tubule: Na
+, K
+, Ca
2+, phosphorous, glucose.
 Acid-base balance: metabolic acidosis when the kidney fails.
 Arterial O2 detection and determining the O2 content of the blood.

Question 2

How much fluid to the kidneys receive, filter, reclaim and produce?

Answer 2

Receive: 20-25% of the total cardiac output (1.1-1.25 L of blood per minute).
 Filter: 180 L filtrate produced per day.
 Reclaim: most of the water that is filtered each day; 1,300 g of NaCl each day; 180 g of glucose each day.
 Produce: 1.2-2 L of urine a day. This can be higher or lower depending on homeostatic balance.

Question 3

Describe the macro and micro structure of the kidney

Answer 3

11 cm in length, 4 cm in diameter, 140 g in weight.
 Retroperitoneal structure
 Renal capsule: fibrous membrane that holds the various
components of the kidney together and provides some
protection to damage and shock.
 Hilus: renal artery enters, renal vein and ureter leave.
 Cortex (outer layer): red in colour (rich blood supply).
 Renal pyramid (inner layer): paler (less rich in blood
supply) and made of medullary tissue.
 Nephron: the functional unit of the kidney and is where
filtration occurs. Made of the cortical nephron and
juxtamedullary nephron. Drains into the minor and
major calyx, and into the renal pelvis.

Question 4

Describe the structure of the nephron

Answer 4

Glomerulus is surrounded by the Bowman’s capsule
which receives the filtrate as a result of Starlings’ forces
building up in the glomerular capillaries. The filtration
barrier prevents large proteins and erythrocytes from
passing into the filtrate.
 Proximal tubule: 15 mm in length (made of the proximal
convoluted tubule and proximal straight tubule). Does
the majority (2/3 of water absorption, Na
+ and Cl
−
absorption) and most glucose absorption.
 Loop of Henle: involved in regulation of dilute or
concentrated urine, through the counter current compliant mechanism.
 Distal tubule and collecting duct: fine tuning of Na
+ and water absorption.
 Collecting duct has two types of cells:
o Principle cell: Na
+ transporters. Aldosterone on the Na
+ transporter influences Na
+ reabsorption.
o Intercalated cell: aquaporin transporters. Expression of aquaporin is under regulation of ADH.

Question 5

What are the 2 types of nephrons

Answer 5

1. Superficial nephrons
    80-85% of total nephrons
    Glomerulus in outer portion of the cortex.
    Short loops of Henle extend only into the outer region of
   medulla.
2. Juxtamedullary nephrons
    15-20% of total nephrons
    Glomerulus deep in cortex and long loops of Henle extend
   deep into medulla, enabling the kidney to secrete very dilute or
   very concentrated urine.
    Ascending limb has thick and thin regions.

Question 6

What is the vascular supply of the kidney?

Answer 6

The kidneys receive 25% of cardiac output, and this is a lot in
comparison to their size. The large blood supply is for filtration
and reabsorption.
 Venous oxygen saturation is only 90% so oxygen supply is low.
 There can be more than one renal artery. It branches into the interlobular
artery which divides the 5 pyramids of the kidney. They then form the
cortical-radial interlobular artery which subdivide into afferent arterioles
and into glomerular capillaries (where filtration occurs).

Question 7

What are peritubular capillaries

Answer 7

The renal artery leads into the afferent arteriole, forming the glomerular
capillaries of the Bowman’s capsule, which eventually leads
into the efferent arterioles.
 Starlings’ forces in afferent and efferent arterioles
determines the rate of glomerular filtration.
 Blood passes down through the peritubular capillaries which
run in conjunction with nephrons.
 20% of blood is filtered, which can be reabsorbed in
peritubular capillaries. Substances can be secreted into the
tubular filtrate.
 Different volumes of urine are finally excreted.

Question 8

Describe the renal nerves

Answer 8

 Most renal nerves form part of the sympathetic autonomic nervous system.
 Most have vasomotor function (regulate blood flow).
 Renin secretion from afferent arteriolar cells is also controlled by the sympathetic nervous system.
 Kidneys also have a parasympathetic nerve supply but their function is unknown.

Question 9

Explain the calcium and phosphate balance in the kidney

Answer 9

1. Body calcium and phosphate homeostasis
    Ca
   2+ levels in extracellular fluid are regulated by the intestine, kidneys and skeleton.
    Phosphate levels in extracellular fluid are predominantly regulated by the kidneys.
    Kidneys excrete the same quantity of Ca
   2+ and phosphate as the net amount entering the body via the GI tract.
    Intestinal Ca
   2+ and phosphate absorption is increased by calcitriol (endocrine hormone) (1,25(OH)2D3
   ), a vitamin D
   metabolite.
2. The kidney and vitamin D3
    Vitamin D3 is activated in the kidney by the action of the enzyme 1α-hydroxylase.
    Production of 1,25(OH)2D3
   is just one of the kidneys’ endocrine functions.

2.1. Activation of vitamin D3
 Sources of vitamin D (cholecalciferol) include UV light on the skin and the
diet.
 Vitamin D is hydroxylated in the liver, forming 25-hydroxycholecalciferol.
This form of vitamin D is in the highest levels in the body.
 Hydrolysed by 1α-hydroxylase (which is produced by proximal tubules of
the nephron). Levels of this enzyme is regulated by parathyroid hormone.
 Produces 1,25-dihydroxycholecalciferol (calcitriol).
3. Regulation of plasma 𝐂𝐚
𝟐+
 CaSR (calcium sensing receptor) on the parathyroid gland. They release
PTH (parathyroid hormone), which affects the resorption of Ca
2+ and phosphate from the bone, increasing plasma Ca
2+
concentration.
 PTH increases reabsorption of Ca
2+ by the kidney. Decreases phosphate reabsorption.
 Kidney produces 1,25-dihydroxycholelcalciferom (calcitriol) which increases Ca
2+ and phosphate absorption in the
intestines.
 These all lead to an increase in plasma [Ca
2+].

4. PTH and renal phosphate and 𝐂𝐚
   𝟐+ reabsorption
    Proximal tubule: binding of PTH to PTH receptor
   increases cAMP. This causes downregulation of two
   phosphate dependent transporters. They are
   internalised into the cell, reducing absorption into
   the blood.
    Distal tubule: transient receptor (TRPV6 in intestine,
   TRPV5 in kidney) transports Ca
   2+ across the
   basolateral membrane through Ca
   2+ ATPase. TRPV5
   is also under regulation of PTH.

Question 10

How are the kidneys oxygen sensors

Answer 10

 As blood pO2 decreases, the kidney detects this and produces erythropoietin (EPO). 85% of EPO is produced from the
kidneys, by interstitial fibroblasts.
 EPO acts on bone marrow stem cells to increase erythrocyte production, since they only have a 120 day lifespan.
 When erythrocyte levels increase, feedback turns off EPO.

Question 11

What is the role of the juxtaglomerular apparatus

Answer 11

 Renin is secreted by granular cells of the kidney afferent arteriole to control blood pressure and volume.
 Renin increases sympathetic activity and lowers levels of Na
+ back into the distal tubule. Na
+ is sensed by Macular densa
cells.
 Renin is released in response to:
o Reduced pressure in the afferent arteriole.
o Increased sympathetic nervous activity.
o Decreased Na
+ in the distal tubule sensed by the Macula densa cells.

Question 12

Describe the RAAS system

Answer 12

Renin is produced by juxtaglomerular cells and cleaves angiotensinogen into angiotensin I. Angiotensin I passes through
the capillary endothelial cells in the lung, and ACE (angiotensin converting enzyme) converts angiotensin I into angiotensin
II.
 Angiotensin II has several functions:
o Increase Na
+ and H2O reabsorption in the proximal tubule.
o Alter arteriole vasoconstriction
o Acts on the pituitary gland, releasing ADH, causing increased H2O reabsorption.

Question 13

Describe water handling by the kidney

Answer 13

GFR (glomerular filtration rate) is 125 ml/min (180 L/day).
 Water reabsorption in the kidney means that < 1% of volume is
excreted into the external environment.

Question 14

What are some examples of kidney disease

Answer 14

Diabetic neuropathy: accounts for 20% of dialysis patients. Glomerulosclerosis (scarring, expanded interstitium). Kidney
function is seriously affected.
 Polycystic kidney disease: cysts throughout the kidney which originate from the nephron tubules. There are two types of
polycystic kidney disease. The autosomal dominant (1 in 1,000 people) counts for 3-4% of dialysis patients.