case 7 - extra

Question 1

what is the RAAS hormone system primarily regulated by

Answer 1

renal blood flow

Question 2

what is the first stage of RAA

Answer 2

the release of the enxyme renin

Question 3

where is renin released from

Answer 3

granular cells of the renal juxtaglomerular apparatus

Question 4

what are the three factors renin is released in response to

Answer 4

Reduced sodium delivery to the distal convoluted tubule detected by macula densa cells.

Reduced perfusion pressure in the kidney detected by baroreceptors in the afferent arteriole.

Sympathetic stimulation of the JGA via β1 adrenoreceptors.

Question 5

what is the released of renin inhibited by

Answer 5

The release of renin is inhibited by atrial natriuretic peptide (ANP), which is released by stretched atria in response to increases in blood pressure.

Question 6

what is angiotensinogen

Answer 6

a precursor protein produced in the liver and cleaved by renin to form angiotensin 1

Question 7

what happens to this angiotensin 1

Answer 7

it is then converted into angiotensin II

Question 8

what converts it from 1 to 2

Answer 8

angiotensin converting enzyme - ACE

Question 9

where does this conversion happen

Answer 9

mainly in the lungs where ACE is produced by vascular endothelial cells

Question 10

how does angiotensin II exert its action

Answer 10

exerts its action by binding to various receptors throughout the body. it binds to one of two G protein coupled receptors, the AT1 and AT2 receptors. although most occurs via AT1

Question 11

what does AII do to the arterioles

Answer 11

vasocontriction

Question 12

what does AII do to the kidney

Answer 12

stimulates Na+ reabsorption

Question 13

what does AII do to the sympathetic nervous system

Answer 13

increased release of noradenaline

Question 14

what does AII do to the adrenal cortex

Answer 14

stimulates release of aldosterone

Question 15

what does AII release do to the hypothalamus

Answer 15

increases thirst sensation and stimulates ADH release

Question 16

describe AII and the renal artery and afferent arteriole

Answer 16

causes vasoconstriction

voltage gated calcium channels open and allow an influx of calcium ions

Question 17

describe what AII does to the efferent arteriole

Answer 17

vasoconstriction - greater than afferent

activation of the AT1 receptor

Question 18

describe what AII does to the mesangial cells

Answer 18

contraction, leading to a decreased filtration rate

activation of Gq receptors and opening of voltage gated calcium channels

Question 19

describe what proximal convoluted tubule and AII

Answer 19

increased Na+ reabsorption

Increased Na+/H+ antiporter activity and adjustment of the Starling forces in peritubular capillaries to increase paracellular reabsorption

Question 20

what does tubuloglomerular feedback involve

Answer 20

the macula densa

Question 21

what is the macula densa

Answer 21

a collection of densely packed epithelial cells at the junction of the thick ascending limb and distal convoluted tubule

Question 22

where does the macula densa end

Answer 22

As the TAL ascends through the renal cortex, it encounters its ownglomerulus, bringing the macula densa to rest at the angle between theafferentandefferent arterioles.

Question 23

what is an indicator of GFR

Answer 23

The macula densa uses the composition of the tubular fluid as an indicator of GFR.

Question 24

what is indicative of a high GFR

Answer 24

A large sodium chloride concentration is indicative of an elevated GFR.

Question 25

describe the mechanism of e.g increased GFR

Answer 25

Increased arterial pressure causes increased glomerular pressure and plasma flow. This increases the GFR. The plasma colloid osmotic pressure increases to limit the increased GFR. The increased GFR increases the tubular flow to the proximal convoluted tubule This leads to increased reabsorption of water and ions in the proximal convoluted tubule and the loop of Henle. The increased GFR increases the tubular flow to the early distal convoluted tubule. There is increased osmolarity of the tubular fluid (i.e. increased NaCl). This is sensed by the macula densa by an apical Na-K-2Cl cotransporter (NKCC2). The juxtaglomerular cells in the macula densa secrete renin, which results in afferent arteriole constriction. This increases the preglomerular resistance, thus decreasing the GFR and keeping it maintained at a steady level. This is known as TUBULOGLOMERULAR FEEDBACK.

Question 26

what can TPRV5 be regulated by

Answer 26

Parathyroid hormone Vitamin D – the kidneys activate vitamin D which stimulates TRPV5 in the DCT Sex hormones Klotho – this is a protein that’s associated with longevity.

Question 27

what is the genetic mutation version of diabetic nephropathy

Answer 27

podocyte damage

Question 28

what is the difference between nephrotic and nephritic syndrome

Answer 28

Nephrotic Syndrome = this is a disease where there is loss of protein (e.g. proteinurea, hypoalbuminaemia) Nephritic Syndrome = this is a disease where there is loss of blood (e.g. haematourea etc)

Question 29

describe leptin and its MoA

Answer 29

Leptin secretion sends signals to the hypothalamus. This causes inhibition of feeding and increased sympathetic output. The increase of sympathetic output causes B-cells to decrease insulin synthesis and secretion. This leads to increased lipolysis and decreased lipogenesis.

Question 30

what does leptin do to the liver

Answer 30

Leptin decreases gluconeogenesis. Leptin increases glycogenolysis. Leptin increases B-oxidation.

Question 31

what does leptin do to the muscle

Answer 31

Leptin increases glucose uptake. Leptin increases glycogenolysis.

Question 32

what are thiazolidinedions

Answer 32

These are a form of drug used to treat type 2 diabetes. They work by increasing the sensitivity of cells to insulin (that are insulin resistant). These provide: Improvement of fasting plasma glucose. Improvement of lipid profile – lower NEFA/ TG/ cholesterol Improvement of B-cell function

Question 33

what is the mechanism of action of thiazolidinedions

Answer 33

These drugs are PPARϒ agonists. PPARϒ are nuclear hormone receptors that cause an increase in adipogenesis in fat cells. This causes an increase in glucose uptake for adipogenesis, thus reducing the blood glucose level, without the need of insulin secretion. These drugs also activate AMP-Kinase. Once activated, AMPK switches on catabolic pathways that generate ATP, while switching off ATP-consuming processes such as biosynthesis and cell growth and proliferation.

Question 34

what is a sliding scale insulin regimen

Answer 34

refers to the progressive increase in pre-meal or nighttime insulin doses. refers to the progressive increase in dosage based on pre-defined glucose ranges.

Question 35

what is the mechanism of action of Trimethoprim

Answer 35

exerts antimicrobial activity by blocking the reduction of dihydrofolate to tetrahydrofolate, the active form of folic acid, but susceptible organsisms. it has inhibitory activity for most gram positive aerobic cocci and some gram negative aerobi bacilli

Question 36

how does ramipril protect the kidneys

Answer 36

in addition to decreasing angiotensin II and increasing bradykinin levels, ramipril increases the levels of vasodilatory renal medullary neutral lipids and inhibits platelet-derived growth factor-induced proliferation of glomerulus cells. ramipril also decreases transforming growth factor-beta in the kidney

Question 37

what is pyelonephritis

Answer 37

a kidney infection - type of UTI that affects the kidneys

Question 38

what is nephrotic syndrome

Answer 38

a kidney disorder that causes your body to pass too much protein in the urine. it is clinically defined as massive proteinuria responsible for hypoalbuminemia, with resulting hyperlipidemia etc. it is caused by increased permeability through the damaged basement membrane in the renal glomerulus, especially infectious or thrombo-embolic. the glomeruli are damaged and cant properly filter your blood