Block B - Diuretics

Question 1

what is the most important function of the kidneys ?

Answer 1

regulation of H2O and inorganic ion balance such as sodium potassium, this is their most important function!

Question 2

other functions of the kidneys ?

Answer 2

The reabsorption of water is a passive process and they normally follow the movement ions particularly sodium by osmosis.They also are involved in the removal of metabolic waste products from blood and excretion in urine such as urea

Question 3

ADME ?

Answer 3

A - absorption

D - distribution

M - metabolism

E - elimination

Question 4

gluconeogenesis ?

Answer 4

Gluconeogenesis is the is the metabolic process by which glucose is produced from glycogen for catabolic reactions from non-carbohydrate precursors. Glucose is the only energy source used by the brain, testes, erythrocytes, and kidney medulla.

Question 5

endocrine function ?

Answer 5

Endocrine functions for example. renin, erythropoietin, aldosterone which are hormones either derived from the kidney ( renin) or influence the kidney such as aldosterone for sodium and water reabsorption.

Question 6

location of adrenal glands and function ?

Answer 6

The adrenals glands that sit on top of the kidneys, they are responsible for secretion of a number of important hormones.

Each adrenal gland is composed of two endocrine components: a medulla (inner part) that constitutes 20% of the gland and a cortex (outer part) that constitutes the remaining 80%.

Question 7

cortex of kidney ?

Answer 7

Zona Glomerulosa is responsible for releasing mineralocorticoids such as sodium, potassium and water and this is influenced by aldosterone by working on sodium channels within the collecting tubules of the kidney.

Question 8

zona fasciculata ?

Answer 8

The Zona Fasciculata releases glucocorticoids such as the stress hormone cortisol, as well as being important in the glucose homeostasis.

Question 9

Zona reticularis ?

Answer 9

The Zona reticularis is important in releasing the sex steroids such as androgens like testosterone, as well as releasing adrenaline.

Question 10

medulla ?

Answer 10

The medulla releases catecholamines such as adrenaline, noradrenaline and dopamine.

Question 11

Juxtaglomerular cells ?

Answer 11

The juxtaglomerular cells can sense a change in blood pressure.

Question 12

drainage of blood ?

Answer 12

the glomerular filtrate ( soluble elements in blood) drains into Bowman’s space, and then into proximal convoluted tubule. The endothelium has pores to allow small molecules through. Podocytes have negative charge. This and the basement membrane stops proteins getting through into tubular fluid. Macula densa senses GFR by [Na+]. Juxtaglomerular (JG) apparatus includes JG cells that secrete renin. JGA helps regulate renal blood flow, GFR and indirectly, modulates Na+ balance and systemic BP.

Question 13

what is GFR controlled by , how and why?

Answer 13

The GFR is controlled by diameters of afferent and efferent arterioles. They contain sympathetic vasoconstrictor nerves. ADH and RAAS also have an effect on GFR.

Question 14

oncotic pressure ?

Answer 14

Oncotic pressure is the amount proteins within the capsular place that hold water in that compartment.

Question 15

why does pressure occur ?

Answer 15

Pressure occurs due to the presence of water and proteins.

Question 16

increase in GFR ?

Answer 16

If there is an increase in the GFR there is dilation of the afferent arteriole and a constriction in the efferent arteriole. This increases the pressure moving in and the blood hydrostatic pressure which will drive more out. Angiotensin II at low doses will result in efferent arteriole constriction but it has not a lot of effect on the afferent arteriole.

Question 17

reduction in GFR ?

Answer 17

If there is a reduction in the GFR, there is an afferent arteriole constriction by angiotensin II high dose and efferent arteriole dilation by blocking the effects of angiotensin II at low doses.

Question 18

kidneys long term or short term control ?

Answer 18

Kidneys are a long-term blood pressure control they do so by controlling blood volume by sodium excretion and retention. A reduction in renal pressure will result in intrarenal redistribution of pressure and increased absorption of salt and water.

Decreased pressure in renal arterioles increases sympathetic activity and renin production and as a result angiotensin II production.

Question 19

angiotensin II ?

Answer 19

Causes direct constriction of renal arterioles

Stimulation of aldosterone synthesis – sodium absorption and increase in intravascular blood volume

Question 20

how does the kidney effect BP ?

Answer 20

The kidney can affect blood pressure due to the effects of renin. Renin is released from the juxtaglomerular cells that surround the afferent arteriole. It is released in response to a change in renal pressure and this is detected via the stretch receptors. If there is a reduction in pressure, then there is a reduction in the stretch, so the production of renin is increased. The Renin then acts on the liver and causes angiotensin I to be produced and this enters the blood flow. The angiotensin I is picked up by the endothelium cells in the lungs and the ACE (angiotensin converting enzyme) converts the AT I into AT II. The angiotensin II then causes vasoconstriction of the blood vessels and this increases blood pressure. Angiotensin II also stimulates the adrenal cortex to release aldosterone for sodium absorption and increase in intravascular blood volume.

Question 21

what occurs in the cortex of a kidney ?

Answer 21

The cortex contains the filtering and reabsorption occurs by the tubules.

Question 22

location of juxtaglomerular cells and what occurs with them ?

Answer 22

The juxtaglomerular cells that surround the afferent arteriole ( letter A so blood moves in here first) will sense changes in the blood pressure. As there is an increase pressure, there is an increase in stretch and the release of renin decreases. If there is a reduction in pressure, then there is a reduction in the stretch, so the production of renin is increased.

Question 23

Macula Densa ?

Answer 23

The Macula Densa in the cortex is an area that has closely packed specialised cells lining the distal tubule. It is sensitive to the Na levels in the filtrate. The macula densa cells participate in the release of renin from the juxtaglomerular cells.

Question 24

inside bowman’s capsule ?

Answer 24

Inside the Bowman’s capsule it is an area of high pressure, it contains podocytes which filter the blood of water and solubilised elements, the soluble products such as plasma proteins are retained. Elements such as ions of sodium and potassium along with water enter the capsule space of the Bowman’s capsule and pass through the collecting ducts which are part of the proximal convoluted tubule. The blood that hasn’t been filtered then moves out through the efferent arteriole into the systemic circulation.

Question 25

primary role of RAAS ?

Answer 25

RAAS has primary importance in blood pressure, it is activated in response to reduced blood flow.

Question 26

what effect does renal disease have on GFR ?

Answer 26

Renal disease, which decreases GFR has an adverse effect on BP. If GFR is reduced, then this increases renin release from JGC. This increases the circulating angiotensin II levels and aldosterone which can cause inappropriate activation of RAAS, this will drive high blood pressure (hypertension).

Question 27

aldosterone stimulate ?

Answer 27

Aldosterone stimulates Na+ reabsorption and K+ excretion by the renal tubule. Aldosterone exerts indirect negative feedback on RAAS by increasing ECV and by lowering plasma [K+].

Really important in conserving Na+ and water by the passive process of osmosis, but also really good at preventing massive swings in K+ levels.

Question 28

what is a rise in BP accompanied by ?

Answer 28

A rise in blood pressure is accompanied by a rise in the extracellular fluid volume which increase the extracellular circulating volume. This increases pressure at the afferent arteriole, this decreases the production of renin. This is negative feedback system.

Question 29

what is the control centre of osmalarity ?

Answer 29

brain

Question 30

increase in osmalirirty ?

Answer 30

An increase in osmolarity, means that the blood is going to become more concentrated, this would occur in a situation where there is dehydration. This would lead to an increase in thirst , resulting in an increase in the water intake. The osmoreceptors are sensitive and they would lead to the release of arginine vasopressin which is an anti diuretic hormone. This leads to the inhibition of water being released from the kidneys (excretion), so more water is retained. ADH will reduce the number of aqua porins that are present in the distal convoluted tubule as it is being retained to offset the thirst response.

Question 31

drop in arterial pressre sensed by ?

Answer 31

A drop in the arterial pressure will be sensed by the aortic and carotid baroreceptors, there is increased cardiac output which increases vascular resistance. The juxtaglomerular apparatus are stimulated and renin is released from the kidney and angiotensin II is the endpoint which is a potent vasoconstrictor so that blood pressure is increased.

Question 32

what do diuretic drugs counteract ?

Answer 32

Diuretic drugs will counteract the effects of aldosterone and angiotensin II, these can be used a treatment against hypertension - prevent sodium reabsorption

Question 33

sympatholytics ?

Answer 33

opposes the downstream effects of postganglionic nerve firing in effector organs innervated by the sympathetic nervous system (SNS). They are indicated for various functions; for example, they may be used as anti-hypertensives.

Question 34

how do all diuretics work ?

Answer 34

All diuretics work indirectly by preventing the re-absorption of water in the kidneys. Most of them by preventing the reabsorption of sodium in the kidney.

Question 35

loop diuretics such as furosemide ?

Answer 35

Loop diuretics include drugs such as furosemide are commonly supplemented with potassium sparing diuretics such as spironolactone or amiloride.

Question 36

thiazides ?

Answer 36

Thiazides include drugs such as bendroflumethiazide which is a mildly potent diuretic and it is commonly used as an adjuvant , or add on in the treatment of hypertension.

Question 37

potassium sparing diuretics ?

Answer 37

Potassium sparing diuretics- are called ‘weak diuretics ‘ which do not acti directly on sodium channels.

Question 38

what is the functional unit of the kidney ?

Answer 38

he functional unit of the kidney is the nephron, there are a total of about 2.5 million in the 2 kidneys.Each nephron consists of 2 functional components:

The tubular component (contains what will eventually become urine)

The vascular component (blood supply)

Question 39

structure of nephrons in order ?

Answer 39

The structure in order is the glomerulus and bowman capsule, proximal convoluted tubule, loop of Henle, distal convoluted tubule and collecting ducts.

Question 40

what occurs to water in the medullary region ?

Answer 40

When blood is filtered at the beginning it is about 300 milliosmoles, but as it travels through the cortex of the kidney, into the medullary region through the collecting duct system, most of the water is passively reabsorbed and thus the filtrate becomes more concentrated, the osmolality reaches 1200 milliosmoles.

Question 41

wherre is most sodium reabsopred ?

Answer 41

Most of the sodium is reabsorbed in the proximal convoluted tubule, this is the same for a lot of the solutes in urine , such as glucose.

Question 42

henle thick ascending tubule ?

Answer 42

Then the filtrate in the loop of Henle the thick ascending tubule, is where the diuretic furosemide works, it will negate 20% of the sodium being reabsorbed

Question 43

early distal convuluted tubule ?

Answer 43

In the early distal convoluted tubule, this is where the thiazides work. This blocks about 10% of the total amount of sodium that is reabsorbed.

Question 44

collecting ducts ?

Answer 44

In the collecting ducts , this is where the potassium sparing diuretics work which negate between 1 to 5 % of blocking sodium reabsorption.

Question 45

how do loop diuretics work ?

Answer 45

Loop diuretics such as furosemide act principally by inhibiting the Na+/K+/2Cl−co-transporter. One transporter is on the lumen side and the basolateral membrane , by blocking this it blocks sodium , chloride and potassium. Due to this they are potent but a side effect is the effect it has on potassium levels causing hypokalaemia ( low K+ levels) affecting the electrophysiology in the heart and hypomimia.

Question 46

how do thiazide diuretics work ?

Answer 46

Thiazide diuretics, which are the most commonly used diuretic, inhibit the sodium-chloride transporter in the distal tubule. Because this transporter normally only reabsorbs about 5% of filtered sodium, these diuretics are less efficacious than loop diuretics in producing diuresis and natriuresis.

Side effect is the loss of potassium but much less when compared to furosemide.

Question 47

potassium sparing diuretics a?

Answer 47

Potassium sparing diuretics such as Amidoride act on the distal tubule Na+-channel inhibitor. They are aldosterone receptor antagonist! Aldosterone ,increases sodium reabsorption and aldosterone causes the channels and sodium enters the blood and potassium leaves the blood. BY blocking this it maintains the potassium balance but blocks the effects of aldosterone on sodium channels.

Question 48

what is spironlactone and eplerenone ?

Answer 48

aldosterone antagonsists

Potassium-sparing diuretics. competitively binding to the aldosterone receptor. Promote Na+ and H20 excretion in the collecting tubule and duct