case 7 - extra Flashcards
what is the RAAS hormone system primarily regulated by
renal blood flow
what is the first stage of RAA
the release of the enxyme renin
where is renin released from
granular cells of the renal juxtaglomerular apparatus
what are the three factors renin is released in response to
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.
what is the released of renin inhibited by
The release of renin is inhibited by atrial natriuretic peptide (ANP), which is released by stretched atria in response to increases in blood pressure.
what is angiotensinogen
a precursor protein produced in the liver and cleaved by renin to form angiotensin 1
what happens to this angiotensin 1
it is then converted into angiotensin II
what converts it from 1 to 2
angiotensin converting enzyme - ACE
where does this conversion happen
mainly in the lungs where ACE is produced by vascular endothelial cells
how does angiotensin II exert its action
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
what does AII do to the arterioles
vasocontriction
what does AII do to the kidney
stimulates Na+ reabsorption
what does AII do to the sympathetic nervous system
increased release of noradenaline
what does AII do to the adrenal cortex
stimulates release of aldosterone
what does AII release do to the hypothalamus
increases thirst sensation and stimulates ADH release
describe AII and the renal artery and afferent arteriole
causes vasoconstriction
voltage gated calcium channels open and allow an influx of calcium ions
describe what AII does to the efferent arteriole
vasoconstriction - greater than afferent
activation of the AT1 receptor
describe what AII does to the mesangial cells
contraction, leading to a decreased filtration rate
activation of Gq receptors and opening of voltage gated calcium channels
describe what proximal convoluted tubule and AII
increased Na+ reabsorption
Increased Na+/H+ antiporter activity and adjustment of the Starling forces in peritubular capillaries to increase paracellular reabsorption
what does tubuloglomerular feedback involve
the macula densa
what is the macula densa
a collection of densely packed epithelial cells at the junction of the thick ascending limb and distal convoluted tubule
where does the macula densa end
As the TAL ascends through the renal cortex, it encounters its ownglomerulus, bringing the macula densa to rest at the angle between theafferentandefferent arterioles.
what is an indicator of GFR
The macula densa uses the composition of the tubular fluid as an indicator of GFR.
what is indicative of a high GFR
A large sodium chloride concentration is indicative of an elevated GFR.
describe the mechanism of e.g increased GFR
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.
what can TPRV5 be regulated by
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.
what is the genetic mutation version of diabetic nephropathy
podocyte damage
what is the difference between nephrotic and nephritic syndrome
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)
describe leptin and its MoA
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.
what does leptin do to the liver
Leptin decreases gluconeogenesis.
Leptin increases glycogenolysis.
Leptin increases B-oxidation.
what does leptin do to the muscle
Leptin increases glucose uptake.
Leptin increases glycogenolysis.
what are thiazolidinedions
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
what is the mechanism of action of thiazolidinedions
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.
what is a sliding scale insulin regimen
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.
what is the mechanism of action of Trimethoprim
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
how does ramipril protect the kidneys
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
what is pyelonephritis
a kidney infection - type of UTI that affects the kidneys
what is nephrotic syndrome
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
