PSL301: Water 4 Flashcards
Sodium balance
Early humans evolved in a ___ sodium environment
Low
sodium is required for…
normal blood volume, BP, organ perfusion
Inadequate sodium results in…
- shock
- low ECF volume
- low BP
Human kidneys are designed to ____ sodium
retain
what happens when the kidneys retain sodium?
keep blood volume high / constant
Why is high blood pressure such a common problem nowadays?
Kidneys are designed to retain sodium, so now that we are getting a lot of Na in the diet, it leads to problems like hypertension
Possible ways to lose Na
- diarrhea
- sweating
- diuretics
We retain Na in conditions like…
heart failure
What happens if we have too much Na?
- edema / pulmonary edema
- weight gain
- breathing problems
Data for some populations suggest that low Na+ increases risk for…
deaths from cardio events
Which ethnicity is famous for high Na diet?
Japanese
Relationship between Na intake and risk of fatal stroke
Higher intake = higher risk for stroke
Where does dietary salt come from?
- 75% from processed foods
- bread, cheese, soup, sauces, restaurants
- very little from home cooking
Normally, urine sodium =
dietary intake of sodium
Urine sodium decreases if…
there is Na lost from gut (diarrhea) or skin (sweating)
Urine sodium decreases to 0 when…
there is severe loss from the gut or skin
e.g. cholera
What can be used to estimate Na intake?
24h urine collection
How long does it take for the kidneys to adjust to increase Na in the diet?
several days is needed to form a new steady state
what happens if there is a sudden increase in Na from the diet?
ECF volume is large for a few days until kidneys adjust
what happens if there is a sudden decrease in Na from the diet?
ECF volume is small for a few days until kidneys adjust
Dietary sodium is a high risk factor for…
- high BP
- stroke
- heart disease
- kidney disease
reducing Na intake is used as a form of treatment for…
- CHF
- cirrhosis with ascites
- kidney diseases
- diseases that result in edema (all of above)
- hypertension
What sends the kidney signals to increase / decrease Na exretion?
Signals from the vascular system
- intravascular volume
- effective circulating volume
What does not signal the kidneys to adjust Na levels?
serum [Na] concentration
What does serum [Na] affect?
- water balance
- ADH
??
What is effective circulating volume?
How well cardiac output fills the arterial system
When is effective circulating volume low?
- low intravascular volume
- poor heart function
- excessive arterial vasodilation
What is low effective circulating volume sensed by?
cardiovascular receptors
- arterial baroreceptors
- juxtaglomerular apparatus
- atrial stretch receptors
What are possible causes of low intravascular volume?
- diarrhea
- sweating
- hemorrhage
What are possible causes of poor heart function?
congestive heart failure
What are possible causes of excessive arterial vasodilation?
liver cirrhosis (advanced liver disease)
The glomerulus is enclosed by…
Bowman’s capsule
Cells that make up the Bowman’s capsule
granular cells
What goes out of the Bowman’s capsule?
proximal tubule
What goes in and out of the glomerulus?
in: afferent arteriole
out: efferent arteriole
What lies beside the arterioles of the glomerulus?
ascending limb of Henle
What is the purpose of having the ascending limb beside the glomerulus?
allow glomerulus to sense things inside the ascending limb
- feedback regulation
- affect filtration rate, Na retention, etc. of glomerulus
What cells make up the ascending limb that lie next to the glomerulus arterioles?
macula densa cells
what are macula densa cells?
- reabsorptive cells that sense NaCl levels
- sends signals to the glomerulus
- regulates GFR
purpose of renin
angiotensinogen -> angiotensin I
what is the rate limiting step of the RAAS?
renin
angiotensin I
small, inactive AA
where can ACE be found?
on endothelial lining of pulmonary capillaries
ANG II has what effect?
- increase BP
- increase blood volume
- maintain osmolarity
ANG II: what does it do to cause increased BP?
- peripheral arterioles (efferent arteriole) vasoconstrict
- cardiovascular control center in medulla tells cardiovascular system to increase BP
- increased volume
where does ANG II affect?
- arterioles
- cardiovascular center in medulla
- hypothalamus
- adrenal cortex
effect of ANG II on hypothalamus
- release vasopressin (ADH)
- thirst
Overall: more fluid in vessels
effect of ANG II on adrenal cortex
release aldosterone
effect of aldosterone
increase Na+ reabsorption (used to maintain osmolarity)
ANG II stimulates Na+ reabsorption in…
- proximal tubule
- distal convoluted tubule
- collecting duct
How does the body make sure only the efferent arteriole is constricted by ANG II?
AT1 receptors are only present on efferent arterioles
what increases renin secretion?
- low afferent arteriole BP
- active SNS
- low dietary NA
- upright posture = more renin
- reduced ECF volume: diuretic therapy, diarrhea, sweating, blood loss
- reduced effective circulating volume (heart failure, liver cirrhosis)
what senses afferent arterole pressure?
- afferent arteriolar stretch
- macula densa
What senses pressure in the SNS?
baroreceptors
the RAAS has what effect on cardiac myocytes, arteries, mesangium?
release growth factor, which reduces compliance in arteries and kidneys
Mesangium
structure that can be found between the afferent & efferent arterioles.
surrounded by capillaries but outside of capillary lumen.
where is aldosterone secreted?
zona glomerulosa of adrenal cortex
aldosterone is a ___ hormone
steroid
receptor for aldosterone
mineralocorticoid receptor
where can the receptor for aldosterone be found?
cortical collecting duct (intracellular receptor)
mechanism of aldosterone
Changes protein synthesis
- increase Na channels (ENaC)
- increase opening of already present channels
effect of aldosterone
- Na reabsorption
- K excretion
- H excretion
ANP is secreted by… in response to…
atrial myocytes atrial stretch (high BP)
function of ANP
- inhibits collecting duct Na reabsorption
- increase GFR
what does ANP inhibit?
- aldosterone
- SNS
- vasopressin
overall: inhibits collecting duct Na reabsorption
Factors that affect Na excretion
- reduced GFR (small effect)
- ANG II
- aldosterone
- ANP
and others not known yet
what causes decreased ECF volume?
- sweating
- diarrhea
- vomiting
- osmotic diuresis
- diuretics
- blood loss
how much Na is lost per L of sweat?
35 mmol/L
how much Na is lost per L of diarrhea?
100 - 120 mmol/L
bicarbonaturia
excretion of excessive amounts of bicarbonates in the urine
how much Na is in gastric fluid?
10 mM
Na loss in the urine is driven by…
bicarbonaturia
??
what states can be seen when there is an excess of sodium?
- congestive heart failure
- cirrhosis with ascites
- kidney disease
congestive heart failure
low CO
why might congestive heart failure cause Na retension
low CO (low BP) stimulates Na retention
why might cirrhosis with ascites cause Na retension
low arterial resistance lowers effective circulating volume -> stimulates Na retension
ascites
the accumulation of fluid in the peritoneal cavity, causing abdominal swelling
side effects of congestive heart failures
edema, pulmonary edema
What effect does high Na have on the heart?
aggravates heart failure
- fibrosis
- oxygen demand
- reduces peripheral perfusion
What drugs can be used to treat heart failure caused by high Na?
- ACE inhibitors
- angiotension receptor blockers
- aldosterone blocker
ACE inhibitor drug
ramipril (-pril)
angiotension receptor blockers drug
losartan (-artan)
aldosterone blocker drug
spironolactone
ramipril, losartan, and spironolactone can be used to treat…
- congestive heart failure
- hypertension
- slow progression of chronic kidney disease
- reduce protein loss in CKD
How to treat someone who has extremely low ECF due to high Na loss?
- IV sodium and water
- isotonic saline
- give something to drink: has salt, glucose, K, alkali
isotonic saline is…
150 mmol/L of Na in water
What does the WHO have to treat those who have severe diarrhea?
oral rehydration fluid:
- NaCl
- glucose
- KCl
- sodium citrate
why is glucose included in oral rehydration fluid?
Na is absorbed through SGLT 1 with glucose
antagonizing RAAS has major benefits in…
cardiovascular and kidney disease
