Handling Sodium And Hypertension Flashcards
What is the most osmotically effective solute in the ECF?
Na+
The input and output of Na+ is approximately how much per day?
10.5 g/day
How is Na+ lost from the body?
Urine (10g)
Sweat (0.25g)
Faeces (0.25g)
What is the osmotic status of sweat?
Hypo-osmotic
In which part of the nephron can we control how much Na+ is reabsorbed?
DCT
What percentage of sodium is reabsorbed in the PCT?
67%
How will changes in the peritubular capillaries affect the PCT Na+ reabsorption?
Decreased pressure in capillaries = increased reabsorption
Increased pressure in capillaries = decreased reabsorption
Describe what happens to Na+ reabsorption when renal BP increases
Decreased Na-H antiporter and reduced ATPase activity Decreased Na+ reabsorption in PCT Decreased water reabsorption in PCT ECF volume decreases BP decreases
How is Cl- reabsorbed?
Transcellular (active)
Paracellular (passive)
Coupled to pumps and dependent of Na+
What percentage of bicarbonate is reabsorbed in the PCT?
90%
What percentage of Cl- is reabsorbed in the PCT?
60%
Which sodium transporters are present in the PCT?
Na-H antiporter
Na-glucose symporter
Na-AA cotransporter
Na-Pi
Which sodium transporter is present in the loop of Henle?
NaKCC symporter
Which sodium transporter is present in the early DCT?
NaCl symporter
Which sodium transporter is present in the late DCT and CD?
ENaC
Which molecules are reabsorbed up to 100% in the PCT?
Glucose
Amino acids
Lactate
What is the order of molecules reabsorbed as you travel down the PCT?
First = glucose, amino acids, lactate Second = bicarbonate Third = phosphate Fourth = chloride
How is the PCT divided?
3 segments
S1, S2, S3
Describe the glomerulotubular balance
Autoregulation - blunts Na+ excretion in response to GFR changes
Always try to take 67% of whatever is filtered
Higher GFR -> more reabsorption
How come the PCT can regulate how much Na+ it reabsorbs?
Because the PCT has flexibility due to not using all of its transporters all of the time
What is the equation for filtered load?
Filtered load = GFR x concentration
What is the osmotic status of the filtrate at the bottom of the loop?
Hypertonic in comparison to plasma
How does Na+ reabsorption occur in the thin ascending limb?
Relies on the steep gradient of Na+ conc to drive passive reabsorption of Na+
How does Na+ reabsorption occur in the thick ascending limb?
Active (pumped)
What does NKCC2 move?
Na+, K+ and 2Cl- from filtrate into cells
What happens to the ions that pass through NKCC2?
Na+ pumped into interstitium via ATPase
K+ diffuses via ROMK back into the tubule
Cl- diffuses into the interstitium
Which region of the nephron is particularly sensitive to hypoxia?
Thick ascending limb of loop of Henle
Uses the most energy
What is the osmotic status of filtrate leaving the loop of Henle?
Hypo-osmotic in comparison to plasma
Why is the filtrate further diluted in the DCT?
Because active Na+ reabsorption can occur but the water permeability of the DCT is fairly low so water cannot follow
In the late DCt and CD, what does water permeability depend on?
ADH
Describe the ion movement occurring in the early DCT
NaCl enters across apical membrane via NCC transporter (Driven by ATPase in basolateral) Leakage of K+ into interstitium KCC4 transporter moves Cl- into blood Leakage of Cl- into interstitium
Which transporter is sensitive to thiazide diuretics?
NCC transporter (Moves NaCl into cells from filtrate)
Describe the ionic movement in the late DCT
NaCl enters cells via NCC and ENaC
Driven by ATPase in basolateral
(Still has the K+ and Cl- leakage seen in the early DCT)
Which diuretics are ENaC sensitive to?
Amiloride diuretics
Is movement through ENaC electroneutral?
No
The difference drives paracellular Cl- reuptake
Where is the major site for Ca2+ reabsorption?
DCT
How is Ca2+ reabsorbed in the DCT?
Apical calcium transport - Ca2+ enters cell, bound by calbindin, shuttles to basolateral membrane
Transporter across basolateral via NCX
Why is only a small amount of calcium filtered at the glomerulus?
Ca2+ in the blood is usually bound
What are the 2 regions of the collecting duct?
Cortical region and the medullary region
What are the 2 distinct cell types in the CD?
Principle cells
Intercalated cells
What is the role of the principle cells of CD?
Reabsorption of Na+ via ENaC
What is the role of the intercalated cells of CD?
Active reabsorption of Cl-
What are the 2 types of intercalated cells in the CD and what are their roles?
A-IC = secretion of acid B-IC = secretion of bicarbonate
What is the equation for pressure in blood vessels?
Pressure = flow x resistance
What is the equation for mean arterial BP?
MaBP = CO x TPR
What is the equation for cardiac output?
CO = SV x HR
Describe the short term regulation of blood pressure
Baroreceptor reflex - nerve endings in the carotid sinus and th aortic arch are sensitive to stretch
Adjusts sympathetic and parasympathetic nervous stimulation to alter the CO
Adjust sympathetic output to peripheral resistance vessels to alter TPR
Which 2 nerves may be stimulated in the baroreceptor reflex?
Glossopharyngeal nerve
Vagus nerve
Why can’t we use the baroreceptor reflex for sustained BP increases?
The threshold for baroreceptor firing resets
Gets used to the sustained increase
Which responses control medium/long term changes in BP?
Neurohumoral responses
What do the neurohumoral responses try to control?
Na+ balance (ECF volume)
Describe Starling’s law of the heart
More blood volume returning to the heart
Increased stretch
Increased cardiac output
What are the 4 parallel neurohumoral pathways?
RAAS
Sympathetic NS
ADH
Atrial natriuretic peptide (ANP)
What is renin?
A proteolytic enzyme released from granular cells JGA
What factors stimulate the release of renin?
Reduced NaCl to DCT
Reduced perfusion pressure in kidneys (afferent arteriole)
Sympathetic stimulation to JGA
How is angiotensin II made?
Angiotensinogen converted to angiotensin I by renin
Angiotensin I converted to angiotensin II by ACE
(ACE = angiotensin converting enzyme)
What are the effects of angiotensin II?
Aldosterone release from adrenal cortex
Vasoconstriction
Na+ reabsorption in kidneys
What are the 2 types of angiotensin II receptor and which is the main one?
AT1 and AT2
AT1 is the main action
What type of receptor is the ATI receptor?
GPCR
What are the main sites of the AT1 receptor?
Arterioles Kidney Sympathetic NS Adrenal cortex Hypothalamus (increased thirst and ADH release)
What are the direct effects of AngII on the kidneys?
Vasoconstriction of afferent and efferent arterioles
Enhanced Na+ reabsorption at PCT via stimulation of Na-H exchanger in apical membrane
How does aldosterone affect the kidneys?
Acts on principle cells of collecting duct - stimulate Na+ and water reabsorption
Activates apical ENaC and K+ channels (increased expression of ENaC)
Increased basolateral extrusion of Na+ via ATPase
Why might ACE inhibitors lead to a dry cough?
ACE usually breaks down bradykinin and substance P
Bradykinin is increased
Gives a dry cough
What is the major effect of bradykinin?
Vasodilation
What are the end results of ACEi?
Prevent production of AngII
Prevent breakdown of bradykinin
Enhance vasodilation
How does the sympathetic NS act to increase BP?
Vasoconstriction of arterioles (decreased GFR and Na+ excretion)
Directly activates apical Na-H exchanger and basolateral pump in PCT
Stimulates renin release from JG cells
What is the main role of ADH?
Formation of concentrated urine by retaining water to control plasma osmolarity
What stimulates ADH release?
Increased plasma osmolarity
Severe hypovolaemia
What are the effects of ADH?
Increase water reabsorption in CD via AQP 2 channels
Increased Na+ reabsorption in thick ascending limb
Causes vasoconstriction
Describe natriuretic peptides
Act to decrease BP
Synthesised and stored in atrial myocytes
Released in response to stretch (volume sensors)
Promotes natriuresis - loss of blood volume
What are the actions of ANP?
Vasodilation in afferent arteriole increases GFR
More sodium filtered out of the blood
Inhibits some Na+ reabsorption along the nephron
Describe the role of prostaglandins
Local mediators
Act as vasodilators
Enhance GFR and reduce Na+ reabsorption - decrease BP
Buffer excessive vasoconstriction (important when AngII levels are high)
How do NSAIDs work?
Inhibit to COX pathway which is involved in the formation of prostaglandins
Why don’t we give NSAIDs when renal perfusion is compromised?
Can further decreased GFR
Lead to acute renal failure
How does dopamine act in the kidney?
Causes vasodilation to increase renal blood flow
Reduced reabsorption of NaCl (inhibits NH exchanger and Na pump)
What are the stages of hypertension and their boundaries?
Stage 1: greater than or equal to 140/90
Stage 2: greater than or equal to 160/100
Severe: greater than or equal to 180/110
What is primary hypertension?
The cause of the hypertension is unknown
95% of cases
What is secondary hypertension and give some examples?
Where the cause of the hypertension can be defined
Eg. Renovascular disease
Aldosteronism
Cushing’s syndrome
High dose of dopamine causes: vasodilation or constriction?
Vasoconstriction
Even though a lower dose will cause vasodilation
What is Conn’s syndrome?
Aldosterone secreting adenoma
Leading to hypertension and hypokalaemia
Give 2 types of vasodilators used for hypertension.
L type Ca2+ channel blockers
Alpha 1 receptor blockers
How do L type Ca2+ channel blockers work?
Reduced calcium entry to vascular smooth muscle cells
Relaxation of vessel walls
Reduced BP
Why don’t we tend to use alpha 1 adrenoceptor blockers?
They cause postural hypotension
Give 2 diuretics commonly used for hypertension and how they work
Thiazide - inhibit NaCl contransporter in DCT, increased loss of Na+ and water
Spironolactone - aldosterone antagonist
What are the actions of beta blockers?
Block Beta 1 receptors
Decreased SNS to heart
Decreased heart rate and contractility
When do we give beta blockers?
Only used in hypertension if there is also another reason to give them eg. Previous MI
