Regulation and Clinical Assessment of Glomerular Filtration Rate

Question 1

describe the functions of the juxtaglomerular apparatus (2)

Answer 1

1. tubuloglomerular feedback: regulation of GFR by macula densa
2. regulation of the circulating renin-angiotensin-aldosterone system, a major regulator of systemic arterial blood pressure and fluid and electrolyte balance

Question 2

what is secretion of renin by the granular cells in the JGS controlled by? (3)

Answer 2

1. sympathetic nervous system input: beta-1 adrenergic receptors promote renin secretion in response to sympathetic stimulus
2. pressure in afferent arterioles: sensed by baroreceptors; low pressure stimulates renin secretion
3. tubular sodium content: monitored by macula densa, low tubular sodium content stimulates renin secretion

Question 3

define autoregulation of renal blood flow

Answer 3

the kidney’s ability to maintain its perfusion constant despite variations in systemic arterial pressure; allows for a relatively constant renal blood flow and glomerular filtration rate across a wide range of mean arterial pressure, called the autoregulatory range; the 2 mechanisms are the afferent arteriolar myogenic response and tubuloglomerular feedback

Question 4

describe the role of the afferent arteriolar myogenic reflex and tubuloglomerular feedback in the regulation of renal blood flow and glomerular filtration rate

Answer 4

afferent arteriolar myogenic reflex: increased blood flow increases tension in the vascular wall causing reflex vasoconstriction, decreasing blood flow towards normal (decreased blood flow has the opposite effect); fast acting to protect the glomeruli from short term fluctuations in blood pressure

tubuloglomerular feedback: links the rate of glomerular filtration to the flow and NaCl concentration of tubular fluid at the macula densa; is intrinsic to the kidney; monitors flow via bending of cilia; monitors NaCl content via uptake via Na+/K+/2Cl multiporters

Question 5

describe how tubuloglomerular feedback alters GFR

Answer 5

if GFR is too high
1. increased GFR increases tubule flow rate
2. the increased flow in the thick ascending limb decreases NaCl removal from the tubule fluid and this increases NaCl delivery to the macula densa
3. the increased NaCL delivery to the mascula densa initiates tubuloglomerular feedback to decrease GFR

if GFR is too low:
tubular flow/NaCl delivery would decrease, initiating tubuloglomerular feedback, but will increase GFR

Question 6

predict how changes in afferent and efferent arteriolar resistances affect renal blood flow and glomerular filtration rate

Answer 6

RBF:
vasodilation of either arteriole increases RBF; vasoconstriction of either arteriole decreases RBF

GFR:
dilation of the afferent arteriole increases GFR (constriction decreases GFR)
dilation of the efferent arteriole decreases GFR (constriction increases GFR)

Question 7

predict the afferent arteriolar myogenic reflex and tubuloglomerular feedback responses to decreases in blood volume or pressure

Answer 7

1. afferent arterioles vasodilate to increase flow and stimulate renin release
2. macula densa: low BP leads to low glomerular capillary hydrostatic pressure, reducing GFR and decreasing NaCl in tubular fluid, stimulating vasodilation of afferent arteriole to increase RBF and GFR and renin release
3. sympathetic ANS: low BP leads to reflex increase in symp stimulation of JGA via arteriolar baroreceptor reflex; leading to renin release

VASODILATION TO RESTORE RBF AND GFR AND RENIN RELEASE

Question 8

define the process of glomerulotubular balance

Answer 8

accomplished by the juxtaglomerular apparatus, the macula densa monitors the tubular fluid and sends signals that increase or decrease GFR in that nephron as needed to maintain renal function

Phenomenon where Na+ reabsorption in the proximal tubule varies in parallel with the filtered load; 2/3 of the filtered Na+ is reabsorbed even when GFR varies ​

In other words, you can only reabsorb what is being filtered in the glomerulus BUT no matter the amount filtered 2/3 of that will be reabsorbed

Question 9

list the characteristics of the 3 main markers of glomerular filtration rate used in clinical practice (BUN, creatinine, SDMA) and interpret changes in their plasma concentration

Answer 9

all are small molecules that are not protein bound and so are freely filtered

BUN: originates from protein catabolism; concentration depends of GFR, tubular flow rate, but also liver function and dietary protein intake

creatinine: originates endogenously from muscle creatine, does not undergo tubular reabsorption, and the only extrarenal factor that affects its concentration os skeletal muscle mass, which is relatively constant for most animals, so is a better marker of GFR than BUN

SDMA: originates from methylates nuclear proteins from all nucleated cells, does not undergo tubular reabsorption or secretion, and is more sensitive than creatinine for detection of decreased GFR as it is not impacted by changes in lean body mass, but is not as widely available for use yet

Question 10

what is azotemia? what are the 3 types?

Answer 10

a lab abnormality defined as an increase in nitrogenous products (BUN, creatinine, SDMA) due to decreased renal excretion, can be

prerenal azotemia: due to decreased blood flow to the kidneys (dehydration, hemorrhage), circulatory shock, heart failure, etc.

renal azotemia: due to decreased function or number of nephrons (intrinsic renal disease, acute or chronic)

postrenal azotemia: due to urinary tract blockage or rupture