Renal physiology

Question 1

What is the glomerulus?

Answer 1

A network of capillaries at the beginning of the nephron that is fed into by the afferent arteriole. The thin vessel walls of the glomerulus allows the exchange of smaller molecules, fluid and waste to pass into the tubule.

Question 2

Describe the different pressures inside and around the glomerulus.

Answer 2

There is a hydrostatic pressure within the glomerulus exerted by the systemic blood pressure to push these molecules out.
There is also an osmotic pressure of the proteins within the capillaries attempting to pull water into the bloodstream.

There is also a capsular hydrostatic pressure due to the filtrate attempting to drain and it can be backed up and exerting a pressure to try and push filtrate back into the glomerulus.
There is also a capsular osmotic pressure, however this should be zero as no plasma proteins should be filtered across the membrane and present in the tubule.

Question 3

What is the overall pressure across the membrane from the glomerulus to the tubule?

Answer 3

There should be a net filtration pressure of approximately 10 mL of mercury.

Question 4

What is the net filtration pressure proportional to?

Answer 4

It is directly proportional to the glomerular filtration rate (ideally 125mL/min)

Question 5

What is glomerular filtration rate a measure of?

Answer 5

The volume of fluid per unit of time is being filtered across glomerular filtration membrane.

Question 6

Which substances can and can’t pass across the glomerular filtration membrane?

Answer 6

Substances that can pass across the glomerular filtration membrane:
Water
Nitrous waste products (urea)
Nutrients (amino acids and glucose)

Substances that can’t:
Blood cells
Albumins
Platelets

Question 7

What are nephrons?

Answer 7

Nephrons are functional units of the kidney. They are not cells, within each nephron they are different cells that make up the functional unit.

Question 8

How many nephrons are present in each kidney? When may you see a decrease?

Answer 8

1.2 million in each kidney

Natural decrease in the number of nephrons with age (also a natural decline in renal function), hypertension and CKD

Question 9

What are the main components of the nephron and describe the movement of filtrate around the nephron?

Answer 9

Filtrate that is able to be absorbed across the glomerular filtration membrane into the Bowman’s capsule. The filtrate here is a similar composition to plasma without the large plasma proteins such as albumin. The filtrate is passed through the proximal convoluted tubule into the loop of Henle, first passing down the descending limb and then up the ascending limb. The ascending limb consists of both a thin and thick luminal region. The filtrate then passes through the distal convoluted tubule and into the collecting duct which all nephrons feed into in production of urine as this feeds into the bladder.

Question 10

What are the main functions of the kidney?

Answer 10

Maintaining extracellular blood pressure and volume
Regulation of osmolality
Maintenance of ion balance
Homeostatic regulation of pH
Excretion of waste
Endocrine function: production of hormones such as renin, erythropoietin and the active form of Vitamin D
Gluconeogenesis in times of starvation

Question 11

Describe the physiology of the Bowman’s capsule.

Answer 11

It is a cup like structure which encompasses the bundle of capillaries known as the glomerulus which is fed into by the afferent arteriole and leaves the efferent arteriole.
It consists of two layers of epithelial cells—the outer parietal and the inner visceral layer. The epithelial cells that form the parietal layer are simple squamous epithelium whilst the visceral layer of Bowman’s capsule are known as podocytes.

Question 12

What are the four main steps in urine formation?

Answer 12

Filtration
Reabsorption
Secretion
Excretion

Question 13

Define reabsorption.

Answer 13

The movement of water and solutes from the nephron back into the bloodstream (circulation).

Question 14

Define secretion.

Answer 14

Movement of water and solutes from the bloodstream back into the nephron.

Question 15

What does the efferent arteriole form?

Answer 15

The efferent arteriole forms the vasa recta which are capillaries which follow the tube of the nephron. The vasa recta enables the reabsorption of water and solutes back into the bloodstream in addition allowing the secretion of products from the bloodstream back into the nephron.

Question 16

What are the two electrolytes responsible for maintenance of blood pressure?

Answer 16

Sodium and water

Question 17

What are the two electrolytes responsible for the maintenance of acid-base balance?

Answer 17

Hydrogen and bicarbonate

Question 18

What is reabsorbed in the proximal convoluted tubule?

Answer 18

Sodium
Chloride
Potassium
Glucose
Amino acids
Urea
Bicarbonate
Water
Calcium

Question 19

What is secreted within the proximal convoluted tubule?

Answer 19

Creatinine
Drugs
Hydrogen ions

Question 20

Which transporters are found in the proximal convoluted tubule?

Answer 20

Sodium-glucose co-transporter on the apical surface, reabsorbs sodium and glucose into the cell facilitated by sodium ions moving down their concentration gradient. GLUT-2 is found on the basolateral membrane and enables reabsorption of both ions into the bloodstream.

Sodium is also reabsorbed by the Na+/H+ exchanger where sodium ions are pumped into the cells in exchange for the secretion of hydrogen ions.

The intercellular concentration of sodium ion low, to enable to the ions to continue moving into the cell down their concentration gradient by the Na+/K+ ATPase which pumps 3 sodium ions into the bloodstream and 2 potassium ions into the cells from the bloodstream facilitated by ATP.

Question 21

Explain the processes that occur within the proximal convoluted tubule to maintain the acid-base balance?

Answer 21

The acid base balance is maintained by two ions: hydrogen ions and bicarbonate ions.

Hydrogen ions are secreted here, by the Na+/H+ exchange and whilst bicarbonate ions are reabsorbed.

Hydrogen ions within the lumen of the nephron react with bicarbonate ions forming carbonic acid (H2CO3). Carbonic anhydrase, carbonic acid is then converted to water and carbon dioxide. As a gas, carbon dioxide can diffuse into the cell and into the bloodstream.

Water and carbon dioxide present within the cell can undergo the reverse reaction, forming carbonic acid and then hydrogen and bicarbonate ions.

Bicarbonate ions can be absorbed into the bloodstream by the sodium-bicarbonate co-transporter (symporter) kNBC1 on the basolateral membrane. This is a sodium dependent process.

Question 22

What is reabsorbed in the descending loop of Henle and how?

Answer 22

Water as the squamous epithelial cells that make up the descending loop of Henle contain aquaporins, enabling the reabsorption of water.

Question 23

What is reabsorbed in the ascending loop of Henle?

Answer 23

Sodium
Chloride
Potassium

Question 24

Which transporters are found in the ascending limb of Henle?

Answer 24

On the apical surface a tri-symporter NKCC1 transports one sodium, two chloride and one potassium from the lumen into the cell. A K+/Cl− cotransporter on the basolateral membrane enables both ions to move into the bloodstream.
Whilst sodium is transported into the bloodstream by the Na+/K+ ATPase on the basolateral membrane.

There are also passive channels on the apical surface allowing the inward movement of sodium ions into the cells and the outward movement of potassium ions into the lumen- nephron.

Question 25

What is reabsorbed in the distal convoluted tubule?

Answer 25

Sodium
Chloride
Calcium
Magnesium
Bicarbonate

Question 26

What is secreted within the distal convoluted tubule?

Answer 26

Hydrogen ions
Potassium

Question 27

Which transporters are found in the distal convoluted tubule?

Answer 27

On the apical surface there is a Na+/Cl- co-transporter, in which both ions are absorbed into the cell, facilitated by the downstream gradient of sodium. On the basolateral membrane sodium is then transported into the bloodstream by the Na+/K+ ATPase and chloride diffuses through chloride ion channels.

Potassium can passively enter the nephron by potassium ion channels.

Calcium and magnesium are reabsorbed by paracellular diffusion.

Question 28

What is reabsorbed within the collecting duct?

Answer 28

Water
Urea
Sodium
Chloride

Question 29

Which transporters are found in the distal convoluted tubule/collecting duct?

Answer 29

Both on the apical and basolateral membrane there are Na+/H+ exchangers, enabling the reabsorption of sodium into the bloodstream and secretion of hydrogen ions into the lumen of the nephron.

A similar acid-base process occurs as in the proximal convoluted tubule. Hydrogen ions within the nephron react with bicarbonate ions forming carbonic acid, which is broken down in water and carbon dioxide by carbonic anhydrase. Both water and carbon dioxide can freely diffuse into the cell in which they undergo the reverse process producing hydrogen and bicarbonate ions.

However this time bicarbonate ions can be reabsorbed into the bloodstream by a Cl⁻/HCO₃⁻ exchanger, where chloride ions enter the cell in exchange for bicarbonate ions.

Question 30

Which transporters are just found in the collecting duct rather than in addition to the distal convoluted tubule also?

Answer 30

Aquaporins, which allow the final reabsorption of water, increasing the osmolality of urine and solute concentration.

Question 31

What is ADH? What is its function?

Answer 31

ADH- anti-diuretic hormone or vasopressin is a posterior pituitary hormone that is released in response to high serum osmolarity detected by osmoreceptors in the hypothalamus.
This increases the expression of aquaporins, increasing water reabsorption with the aim to reduce the serum osmolality in homeostatic regulation.

Question 32

What is aldosterone? What is its function?

Answer 32

Aldosterone is a mineralocorticoid hormone produced in the zona glomerulosa of the adrenal cortex that influences water and salt regulation in the body by acting on the late distal convoluted tubule and collecting duct.
Aldosterone promotes sodium reabsorption, potassium excretion and also influences the acid-base balance.

Question 33

What is aldosterone released in response to?

Answer 33

A increase in the plasma concentration of angiotensin III (metabolite of angiotensin II)

Increase in plasma angiotensin II, adrenotropic hormone , or potassium levels, which are present in proportion to plasma sodium deficiencies

Question 34

What are the downstream effects of aldosterone?

Answer 34

Aldosterone ultimately acts on the nuclear mineralocorticoid receptors within the principal cells of the distal tubule and collecting duct of the kidney nephron.

It upregulates and activates the basolateral Na+/K+ pumps, to create a concentration gradient enabling reabsorption of sodium (and water) into the blood and the secretion of potassium ions.

Aldosterone upregulates epithelial sodium channels (ENaCs) in the collecting duct increasing apical membrane permeability for Na+ and thus absorption (chloride is also reabsorbed to maintain the balance).

Aldosterone also stimulates the secretion of K+ into the tubular lumen.

Aldosterone stimulates secretion of H+ via the H+/ATPase in the intercalated cells of the collecting tubules

Aldosterone upregulates expression of NCC in the distal convoluted tubule chronically and its activity acutely

Question 35

What are the components of urine?

Answer 35

95% water, metabolites, nitrogenous waste products

Question 36

What are diuretics?

Answer 36

Diuretics are substances that increase the excretion of sodium (with an accompanying anion, usually chloride) and water by inhibiting sodium reabsorption.
Diuretics act on the nephron, and are used in the treatment of oedema and high blood pressure.

Question 37

What are the different types of diuretics?

Answer 37

Thiazide diuretics
Loop diuretics
Aldosterone antagonists/Mineralocorticoid receptor antagonists
Potassium sparing diuretics

Question 38

What are some examples of thiazide diuretics?

Answer 38

Bendroflumethiazide
Hydrochlorothiazide

Related:
Indapamide
Metolazone
Chlortalidone

Question 39

Where do thiazide diuretics act in the nephron?

Answer 39

On the distal convoluted tubule

Question 40

What is the mechanism of action of thiazide diuretics?

Answer 40

Inhibits the Na+/Cl- (NCC) co-transporter present on the distal convoluted tubule which is responsible for 5-10% of the reabsorption of filtered sodium.
This results in an increased excretion of sodium, potassium (due to sodium-potassium exchange system), chloride and water.
However the effect is limited due to 90% of sodium reabsorption occurring before reaching the distal convoluted tubule.
Natriuresis (excretion of sodium) due to osmosis also promotes water loss, overall decreasing the ECF volume.

Question 41

What are some examples of loop diuretics?

Answer 41

Furosemide
Bumetanide
Torasemide

Question 42

What are some of the indications of thiazide diuretics?

Answer 42

Hypertension
Mild heart failure (loop diuretics are used in preference)
Severe resistant oedema (Metolazone can be used together with loop diuretics)
To prevent stone formation in idiopathic hypercalciuria
Nephrogenic diabetes insipidus

Question 43

Where do loop diuretics act in the nephron?

Answer 43

Predominately at the ascending limb of Henle
But also has effects at the proximal and distal tubule.

Question 44

What is the mechanism of action of loop diuretics?

Answer 44

Loop diuretics competitively compete with chloride ions at the Na+/K+/2Cl– cotransporter (NKCC2) on the apical membrane of the ascending limb of Henle.
This prevents the reabsorption of sodium increasing its excretion alongside water, chloride, magnesium, calcium, hydrogen, and potassium ions.
Potassium and hydrogen ions are excreted due to increased sodium within the filtrate by the distal convoluted tubule.
Loop diuretics also decrease the excretion of uric acid.

Question 45

What are some of the indications of loop diuretics?

Answer 45

Loop diuretics are used cautiously in combination with dietary salt restriction and often other classes of diuretics, in the treatment of salt and water overload associated with:
Pulmonary oedema
Chronic heart failure
Cirrhosis of the liver complicated with ascites
Nephrotic syndrome
Renal failure

Treatment of hypertension complicated by renal impairment (thiazides preferred if renal function is reserved)
Treatment of hypercalcaemia after replacement of plasma volume with IV NaCl solution

Question 46

What are some examples of potassium sparing diuretics?

Answer 46

Amiloride
Triamterene

Question 47

Where do potassium sparing diuretics act in the nephron?

Answer 47

Distal convoluted tubule and collecting ducts

Question 48

What is the mechanism of action of potassium sparing diuretics?

Answer 48

Directly blocks the ENaC, inhibiting sodium reabsorption in the late distal convoluted tubule and collecting ducts. This therefore overall results in a reduced sodium and water reabsorption, whilst reducing the potassium excretion.
These are often co-prescribed with thiazide diuretics to reduce their hypokalaemic effect.

Question 49

What are some examples of aldosterone antagonists/mineralocorticoid receptor antagonists?

Answer 49

Spironolactone
Eplerenone

Question 50

Where do aldosterone antagonists act in the nephron?

Answer 50

Distal convoluted tubule

Question 51

What is the mechanism of action of aldosterone antagonists?

Answer 51

They competitively bind to receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule. This therefore reduces sodium reabsorption, causing an increase in sodium and water excretion and reducing potassium excretion, therefore also has a potassium-sparing effect.
However drugs that act as an aldosterone antagonist has limited diuretic effect due to the site only being responsible for the reabsorption of 2% of filtered sodium.

Question 52

What are some of the indications of aldosterone antagonists?

Answer 52

Heart failure
Primary hyperaldosteronism (Conn’s syndrome)
Resistant essential hypertension (esp. low renin hypertension)
Secondary hyperaldosteronism caused by hepatic cirrhosis complicated with ascites

Question 53

Where are the kidneys found in the body?

Answer 53

With both the size of a fist, the kidneys are located at the back of the abdominal cavity, with the right kidney being slightly lower than the left due to the presence of the liver

Question 54

What are the external layers of the kidney?

Answer 54

Renal fascia - dense, elastic, connective tissue
Perirenal fat capsule - a fat pad surrounding the kidneys in the retroperitoneal space
Renal capsule- fibrous connective tissue

Question 55

What are the internal layers of the kidney?

Answer 55

Renal cortex
Renal medulla
Renal pelvis

Question 56

Which cells form the proximal convoluted tubule?

Answer 56

The proximal convoluted tubule (PCT) has a high capacity for reabsorption, hence it has specialised features to aid with this. It is lined with simple cuboidal epithelial cells which have a brush border to increase surface area on the apical side

Question 57

Which cells form the descending loop of Henle?

Answer 57

The epithelium of the thick segment is low simple cuboidal epithelium and the epithelium of the thin segment is simple squamous.
I believe this is the same for the ascending loop of Henle.

Question 58

Which cells form the distal convoluted tubule and the collecting duct?

Answer 58

Principal cells and intercalated cells

Question 59

What is the function of the principal cells?

Answer 59

Reabsorption of sodium ions and excretion of potassium ions

Question 60

What is the function of the intercalated cells?

Answer 60

Intercalated cells are involved in acid-base regulation by secreting or reabsorbing hydrogen ions (H+) and bicarbonate ions (HCO3-)

Question 61

What is renin? What is it secreted by?

Answer 61

Renin is a angiotensinogenase, is an aspartic protease protein and enzyme secreted by the kidneys/
It is primarily secreted by specialized cells known as juxtaglomerular (JG) cells located near the glomerulus of the kidney.

Question 62

Which stimuli triggers juxtaglomerular cells to secrete renin?

Answer 62

A decrease in arterial blood pressure sensed by baroreceptors (pressure sensing receptors).
A decrease in sodium load delivered to the distal tubule. This load is measured by the macula densa of the juxtaglomerular apparatus.
Sympathetic nervous system activity, which also controls blood pressure, acting through the β1 adrenergic receptors

Question 63

Briefly describe the RAAS system.

Answer 63

A drop in blood pressure or fluid volume results in the secretion of renin. Renin cleaves angiotensinogen produced by the liver to form angiotensin I.
ACE (angiotensin converting enzyme) is released from the lungs converting angiotensin I to angiotensin II. Angiotensin II acts on blood vessels causing vasoconstriction but also acts on the adrenal cortex triggering the release of aldosterone which acts on the nephron, stimulating the reabsorption of salt and water.