Renal 2 Flashcards

Renal Lectures 5-7

1
Q

organ systems involved in integrative process of maintaining fluid and electrolyte balance

A

respiratory, CV, renal, behavioural responses

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2
Q

T or F: 2/3 of body water is ECF

A

F: intracellular

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3
Q

diuresis osmolarity

A

removal of excess urine (dilute urine), 50 mOsM

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4
Q

if kidneys need to conserve water, what urine is produced, osmolarity

A

low volume of conc urine, up to 1200 mOsM

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5
Q

renal cortex is what osmolarity to plasma

A

isosmotic

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6
Q

renal medulla is what osmolarity to plasma

A

hyperosmotic, progressively more concentrated as filtered through nephron

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7
Q

vasopressin does what

A

alter membrane permeability to water by inserting or removing water pores in the apical membrane in collecting duct, signals from posterior pituitary hormone vasopressin (AVP), antidiuretic hormone (ADH)

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8
Q

T or F: insertion of AQP2 is graded

A

T: depends on amount of vasopressin (AVP) present

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9
Q

4 steps of AQP2 channel insertion

A
  1. vasopressin released from posterior pituitary travels via blood and binds to membrane receptor on blm
  2. receptor activates cAMP second messenger system
  3. cells insert AQP2 water pores into apical membrane via exocytosis of storage vesicles
  4. water enters cell via AQP2 and diffuses into blood via osmosis
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10
Q

what stimulates vasopressin secretion

A

decreased blood pressure:
carotid and aortic baroreceptors -> sensoru neuron to hypothalamus

decreased atrial stretch bc of low blood volume:
atrial stretch receptor-> sensory neuron to hypothalamus

osmolarity greater than 280mOsM:
hypothalamic osmoreceptors -> interneurons to hypothalamus

all = increased vasopressin synthesis in hypothalamus then stored and released from posterior pituitary

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11
Q

what cells produce AVP? how is it secreted?

A

magnocellular neurosecretory cells (MNC’s) produce and release AVP

-osmolarity monitored by osmoreceptors neurons. stretch sensitive that increase firing as osm increase (shrink, opposite of normal stretch receptors)

  • signal to MNCs, APs fire in the MNCs causing release of AVP containing vesicles

-baro and atrial receptors also signal

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12
Q

what creates the hyperosmotic interstitium and why isn’t it reduced as water is reabsorbed?

A
  1. the loop of Henle is a countercurrent multiplier - kidneys transfer water and solute instead of heat
  2. Urea contributes to hyperosmotic interstitium
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13
Q

The renal countercurrent exchange system- two components

A

multiplier: loop of henle, create hypertonic interstitium

exchanger: peritubular capillaries (vasa recta), prevent dilution of the hypertonic interstitium

-as filtrate enters descending limb, progressively more conc as it loses water

  • the ascending limb pumps out solutes and filtrate becomes hyposmotic

-blood in vasa recta removes water leaving the loop

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14
Q

countercurrent multiplier osmolarities

A

start of descending limb: 300 = interstitium
middle (bottom): 1200 bc water pumped out
ascending limb: 100, solutes pumped out, no AQP2, becomes hyposmotic

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15
Q

% of reabsorption taking place in ascending limb

A

25% of Na and K

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16
Q

what transporter actively transports solutes to create countercurrent multiplier

A

NKCC transporter: Na, K, 2 Cl
apical membrane (out of tubule, through epithelial cells, to interstitium to vasa recta)

active transport: uses Na gradient energy

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17
Q

how does urea contribute to the hyperosmotic interstitium

A

about half of solute in interstitium is urea

  • 50% urea reabsorbed in the proximal tubule
  • 50% of urea is secreted back into loop of henle
  • 30% reabsorbed in distal portion of nephron
  • 50% reabsorbed from end of collecting duct

makes recycling loop

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18
Q

homeostatic mechanisms to maintain mass balance - response to salt ingestion

A

no change in volume, increase osmolarity

  1. Vasopressin secretion
    - increase water reabsorption = kindeys conserve water in body

a. increase water reabsorption -> increase ECF -> increase bp -> CV reflexes (rapid response)

  1. thirst
    - increase water intake
    a. “”
    b. increase ECF volume -> kidneys excrete salt and water = osmolarity returns to normal + volume and bp (slow response)
19
Q

what endocrine pathway helps control Na balance

A

renin-angiotensin-aldosterone system

20
Q

what does aldosterone do

A

aldosterone is a steroid hormone that is regulates Na reabsorption and K secretion

targets end of distal tubule and cortex/ start of collecting duct

zona glomerulosa cells

21
Q

what cells does aldosterone act on

A

principal cells

22
Q

principal cells vs intercalated cells

A

2 types of cells in collecting duct

principal cells: Na and water regulation
intercalated: acid-base balance, type A and B

23
Q

5 steps of aldosterone pathway

A
  1. aldosterone combines with cytoplasmic receptor in cell
  2. hormone-receptor complex initiates transcription in nucleus
  3. translation and protein synthesis makes new protein channels and pumps
  4. aldosterone-induced proteins modulate existing channels and pumps
  5. Results: increased Na reabsorption and K secretion
24
Q

what is the cytoplasmic aldosterone receptor called

A

mineralocorticoid receptor

25
apical membrane solute channel names
Na: epithelial Na channels ENaC K: renal outer medulla K ROMK
26
fast aldosterone response
modulation of existing transporters: increase opening of apical Na and K channels, enhance Na reabsorption and K secretion. Also insert pre-existing transporters - increased Na entry into the cell, speeds up as blm Na/K ATPase leading to increased Na reabsorption - increased Na/K ATPase increases intracellular K leading to increased K secretion
27
slow aldosterone response
hormone ligand complex translocate in to the cell nucleus, binds to hormone response elements that increase transcription of apical Na channels and K channels as well as blm Na/K ATPase, further enhancing Na reabsorption and K excretion
28
aldosterone secretion pathway
1. high K stimulates adrenal cortex directly, protecting from hyperkalemia 2. decreased bp usually controls aldosterone secretion, initiating pathway that results in production of angiotensin 2, triggers release of aldosterone
29
additional modifiers of aldosterone release
1. high osmolarity directly inhibits adrenal cortex release during dehydration 2. abnormally large drops in plasma Na conc directly stimulates aldosterone secretion
30
purpose of renin-angiotensin system (RAS)
multistep pathway to maintain blood pressure, activated when low bp
31
RAS macula densa cells
sense distal tubule flow and release paracrines that affect afferent arteriole diameter, make up tubule
32
RAS granular cells
secrete renin enzyme, also known as juxtaglomerular cells, make up capillary
33
, first stop and 3 stimuli of RAS
step 1: renin secretion three stimulus: 1. low bp in renal arterioles causes granular cells to secrete renin 2. sympathetic neurons activated by CV control centre when bp decreases terminate on granular cells and stimulate renin 3. paracrine feedback (prostaglandins) from macula densa cells signal to granular cells to secrete renin
34
what is renin's main role
convert an inactive plasma protein angiotensin to angiotensin 1
35
angiotensin 1 pathway steps
1. angiotensin 1 is converted to 2 by angiotensin converting enzyme (ACE) 2. ANG2 travels to adrenal cortex and stimulates production of aldosterone
36
ANG2 effects (5)
1. increase vasopressin secretion (initiate by ANG receptors in hypothalamus) 2. stimulates thirst 3. potent vasoconstrictor 4. ANG2 receptors activated in CV control center increase sympathetic output to heart and blood vessels 5. increase proximal tubule Na reabsorption -stimulate an apical Na/H exchanger - increase water reabsorption ALL mechanisms help restore bp
37
how do pharmaceutical companies utilize the RAS pathway for treating high bp
now use ACE inhibitors prevent conversion of ANG1 to 2 which leads to relaxation of vasculature and lowers bp other options include: AT receptor antagonists, renin inhibitors
38
what is ANP, where is it
atrial natriuretic peptide (ANP) promotes Na and water excretion peptide hormone produces and secreted by specialized myocardial cells in the atria
39
what does ANP do
increase in blood volume causes increased stretch of atria, causing specialized myocardial cells to release ANP
40
what's ANP receptor
enzymatic membrane bound receptor acting through cGMP second messenger system
41
ANP effects on kidneys
-relax afferent arteriole (increase GFR) -reduce renin release from granular cells = reduce aldosterone and ANG2 - reduce NA reabsorption in collecting duct
42
ANP effect on hypothalamus
reduce AVP release, inhibit thirst
43
ANP effect on adrenal cortex
inhibits aldosterone release
44
ANP effect on medulla
act in CVCC (control centre) to decrease bp