Week 4 - Volume and blood pressure control Flashcards
How can sodium ions affect blood pressure?
- Sodium is the major cation of the ECF
- The amount of Na+ determines the ECF volume
- In turn, this determines the volume of plasma and hence blood pressure
What causes expansion of the extracellular fluid?
- If Na+ excretion is less than intake, then a patient is in positive sodium balance
- Extra Na+ ions are retained in the body, primarily in the ECF
- When Na+ content of the ECF increases, there is a corresponding increase in ECF volume
- – Water from the nephron is drawn out
- – Blood volume and arterial pressure increase
- – Oedema may follow
What causes contraction of the extracellular fluid?
- If sodium ion excretion is greater than ingestion, then a patient is in negative sodium balance
- Excess Na+ is lost from the body
- The Na+ content in the ECF decreases
- – Water remains in the nephron
- – Decrease in ECF volume
- – Blood volume and arterial pressure decrease
What happens to Na+ ions in the PCT?
- 100% of the Na+ is filtered in the glomerulus
- 67% is reabsorbed in the PCT
- – This percentage is always reabsorbed, regardless of the actual amount that is filtered (glomerular tubular balance)
- Na+ reabsorption is mainly active
- – Driven by 3Na-2K-ATPase pumps on the basolateral membrane
- Different segments of the tubule have different types of Na+ transporters and channels in the apical membrane
What happens at different points of the PCT and what channels are found there?
Section 1 of the PCT: - Na+ is cotransported with glucose - Na-H exchange - Co-transport with AA/carboxylic acids - Co transport with phosphate - Aquaporin - [Urea and Cl-] increase down this section, compensating or the loss of glucose - Increasing [Cl-] creates a concentration gradient for chloride reabsorption Section 2/3 of the PCT: - Na+ and water reabsorption - Na-H exchanger - Paracellular Cl- reabsorption - Transcellular Cl-reabsorption - Aquaporin
What type of reabsorption occurs in the PCT?
Isosmotic reabsorption:
- The PCT is highly water permeable
- Allows reabsorption to be isosmotic with plasma
- Reabsorption is water is driven by:
- – Osmotic gradient due to solute reabsorption
- – Hydrostatic force in the interstitium
- – Oncotic force in the peritubular capillary (Due to the loss of 20% filtrate at the glomerulus, but cells and proteins remained in the blood)
What is the glomerulotubular balance?
The balance between GFR and the rate of reabsorption of solutes
- Must be kept as constant as possible
- If GFR increases, the rate of reabsorption must also increase
- It blunts sodium excretion
- It is a response to any GFR changes that occur despite autoregulation
What happens if the ECF volume increases?
- Cardiac output will increase
- This will cause an increase in arterial pressure
- This in turn will increase GFR
What happens in the descending limb?
It reabsorbs water but not NaCl
- The increase in intracellular concentrations of Na+ set up by the PCT allows for paracellular reuptake of water
- This concentrates the Na+ and Cl- in the lumen of the descending limb, ready for active transport in the ascending limb
What happens in the ascending limb?
It reabsorbs NaCl but not water
- Known as the diluting segment
- Tubule fluid leaving the loop is hypo-osmotic compared to plasma
- Impermeable to water, as it has tight junctions
- Thin ascending limb:
- – Sodium reabsorption is passive and occurs paracellularly
- – The gradient is created by water reabsorption in the descending limb
- Thick ascending limb:
- – NaCl is transported from the lumen into the cells by NaKCC2
- – Na+ then moves into the interstitium due to the action of 3Na-K-ATPase
- – K+ ions diffuse back into the lumen via ROMK
- – Cl- ions move into the interstitium
- – This region uses more energy than any other region of the nephron and is particularly sensitive to hypoxia
- – NaKCC2 is the target of loop diuretics
What happens in the early DCT?
- Water permeability is fairly low
- The active reabsorption of Na+ results in dilution of the filtrate
- Hypo-osmotic fluid enters from the loop
- ~5-8% of Na+ is actively transported by the NaCC transporter, driven by 3Na-2K-ATPase
- – This transporter is sensitive to thiazide diuretics
- The DCT is also a major site of calcium reabsorption, via PTH
- The fluid that leaves is more hypo-osmotic than the fluid that entered
What cells are found in the later DCT/collecting duct?
There are 2 distinct cell types:
- Principle cells
- – 70% of the cells
- – Reabsorption of Na+ via epithelial Na+ channel (ENaC)
- – Driven by 3 Na-2K-ATPase
- – Provides lumen charge
- – Electrical gradient for paracellular Cl- reabsorption
- – Potassium secretion into the lumen
- – Variable water uptake via aquaporin 2
- – Dependent on ADH
- Type B intercalated cells
- – Active reabsorption of chloride
- – Secrete H+ ions or HCO3-
What are the 4 neurohumoral factors controlling blood pressure?
- Renin-angiotensin-aldosterone system
- Sympathetic nervous system
- Antidiuretic hormone
- Atrial natriuretic peptide
How does sympathetic stimulation affect blood pressure?
High levels of sympathetic stimulation reduce renal blood flow
- Vasoconstriction of arterioles by α1-adrenoceptors
- Increases force/rate of heart contraction β1-adrenoceptors
- Decrease GFR and hence Na+ excretion
- Activates Na/H exchanger in PCT
- Stimulates renin release
(Raises BP)
How does atrial natriuretic peptide affect blood pressure?
- Promote Na+ excretion
- Synthesised and stored in atrial myocytes
- Released from atrial cells in response to stretch
- Reduced effective circulating volume inhibits the release of ANP
— Less filling of the heart so less stretch and hence less ANP released so BP can be maintained - Causes vasodilation of the afferent arteriole
(Lowers BP)
