Lecture 3 Flashcards
(26 cards)
What happens if the salt levels drift 1-2%?
We could die - need to maintain our osmolality.
What happens if a person has a high sodium diet for 5 days?
The salt will go into the body and change the osmolality. The kidneys will begin to excrete more salt. But this is not fast enough - there is a 1-2 day lag. During the lag time the ECF will have more sodium in it. To deal with the extra salt, our bodies need to increase water absorption - retain water so there will be weight gain. This is to maintain constant ECF osmolality. Osmolality will return to normal however there will be a larger ECF volume. Larger ECF volume continues while the high sodium diet continues. Eventually blood pressure increases to the point where salt is lost by pressure natriuresis.
What happens if we give a person pure water (1L)/
Total water volume will increase - both intracellular and extracellular component. This will dilute the salt. The dilution won’t be as extreme. If we to give someone a bag of normal saline, the urine excretion volume hasn’t changed because there isn’t an acute need to change liquid.
What happens if IV fluids contain dextrose?
Glucose is iso-osmotic. However it is metabolised into water.
Describe IV fluids?
Isotonic saline fluids will expand the extracellular component where as hypotonic saline fluids will expand the intracellular component.
Describe starling forces?
These forces govern the movement of water and solutes between plasma and ISF. The capillary wall is a semi-permeable membrane. As you push blood through the capillary there is pressure. The hydrostatic pressure force will push water and solutes out of the blood. Because plasma proteins can’t leave they exert an oncotic pressure which will draw water and salt into the vessel. Two opposing forces.
What is the glomerulus function?
The glomerulus is a leaky capillary tuft - due to endothelial cells being fenestrated. The glomerulus is located between two arterioles. Blood comes into the glomerulus which will create hydrostatic pressure (60mmHg). The proteins in the capillary will provide oncotic pressure (32mmHg). Then there is a capsular hydrostatic pressure (18mmHg). The net filtration pressure is 10mmHg (60 - 32 - 18). Only 20% of plasma volume in the capillaries is filtered. Glomerular function rate (GFR) = 125ml/min.
How do we ensure a constant GFR?
The kidney needs to tightly regulate ECF osmolality and pH for survival. The primary regulator of GFR is changes in hydrostatic pressure.
Describe renal auto regulation?
In healthy individuals changes in systemic blood pressure should change GFR however it doesn’t due to renal auto-regulation. It involves feedback mechanisms that cause either dilation or construction of the afferent arteriole or constriction of the efferent arteriole.
What happens if you constrict the afferent arteriole?
This will decrease blood flow to the glomerulus. Thus you will decrease glomerular hydrostatic pressure. Thus decrease the GFR.
What happens if you dilate the afferent arteriole?
This will increase blood flow to the glomerulus. Thus you will increase the glomerulus hydrostatic pressure. Thus increase the GFR.
What happens if you moderately constrict the efferent arteriole?
Back pressure will be created in the capillary bed, this will increase glomerulus hydrostatic pressure, thus increase GFR.
What are the extrinsic mechanisms of renal auto regulation?
- Renin-angiotensin II will constrict the efferent arteriole which will increases GFR.
- Atrial natriuretic peptide (ANP) will dilate the afferent arteriole, which will increase GFR.
- SNS will constrict the afferent arteriole, this will decrease GFR - occurs during shock.
What are the intrinsic mechanisms of renal auto regulation?
- ‘Myogenic’ - Increase arterial pressure stretches the afferent arterioles inducing it to constrict (to resist the stretch). This will keep GFR stable.
- Tubuloglomerular feedback - macula dense cells monitor NaCl levels in the distal tubule. If the NaCl levels are high they will signal to the afferent arteriole to constrict thus decreasing GFR (returning GFR to stable set point).
Describe the tubuloglomerular feedback?
If the GFR is too high (too much filtration), salt will get pushed all the way down the tubes and will hit the macula dense cells. Paracrine signals will be released, this will construct the afferent arteriole thus decreasing GFR.
Describe the renin-angiotensin mechanism?
If the GFR is low, the macula dense cells will sense less salt. Paracrine signals are released and JG cells will release renin. Angiotensin II is produced and this will cause constriction of the efferent arteriole which will increase GFR. Aldosterone is also released by angiotensin II, this will increase sodium uptake front he distal nephron and thus increase blood volume.
What were to happen if blood pressure were to drop?
Blood pressure decreases, so blood flow to the glomerulus will decrease. This will cause a decrease in hydrostatic pressure and thus a decrease in GFR. First the decrease in hydrostatic pressure will cause a myogenic response, as there is less stretch of the afferent arteriole there will be a decrease int existence of the afferent arteriole therefore there will be an increase in hydrostatic pressure. Second the decrease in GFR will cause there to be a decrease of flow of NaCl to the macula dense cells this will cause tubuloglomerular feedback. This will cause JG cells to release more renin so more angiotensin II is released. This will cause constriction of the efferent arteriole which will cause an increase in GFR.
Describe the proximal tubule?
This is the major site of filtrate reabsorption. 66% of water and inorganic ions are reabsorbed. 90% of bicarbonate is reabsorbed and 100% of glucose and amino acids are reabsorbed.
Describe he transport mechanisms in the proximal tubule?
Transcellular - across epithelial cells:
- Primary active transport, ATP driven.
- Secondary active transport, driven by another gradient:
- Co-transport or symport.
- Countertransport or anti port.
Paracellular - between cells:
Passive.
Predominately in the proximal tubules are Sodium coupled transporters. Therefore Na+/K+/ATPase function is critical. >90% of ATP consumed by the Na+/K+/ATPase pump.
Describe active transport in the early proximal tubule?
The sodium/potasssium ATPase will push sodium out of the cell into the ECF. This will cause sodium to be low in the proximal tubule cell and this will cause a gradient. There is a transporter at the brush border cells. The lumen is high in sodium. As the sodium goes into the cell down the concentration gradient (from lumen to the cell). Water will follow the sodium and pass through the leaky tight junctions paracellularly - known as ‘solvent drag’ where some solutes are reabsorbed. The osmolality of the filtrate remains the same.
Describe bicarbonate?
Bicarbonate is a key pH buffer in the body and needs to be reabsorbed from the filtrate. It cannot diffuse across the cell membrane. Reabsorption depends on carbonic anhydrase (brush border and cytoplasm).
Describe reabsorption of bicarbonate by the proximal tubule?
The sodium hydrogen exchanger will reabsorbs sodium into the cell in exchange for hydrogen which it excretes into the lumen. Hydrogen will then adds to bicarbonate to create carbonic acid which will turn into water and carbon dioxide via carbon anhydrase on the brush border. Carbon dioxide then enters the cell where it is metabolised with water and CA to form carbonic acid where it will become hydrogen ions and bicarbonate. Bicarbonate is them transported across the basolateral membrane.
how does the proximal tubule generate new bicarbonate?
The cells metabolise glutamine to ammonium ion and bicarbonate. The ammonium is secreted into the lumen by a Sodium/NH4+ exchanger. Bicarbonate transported into the blood.
What is falcon syndrome?
The proximal tubules can’t reabsorb bicarbonate, amino acids, glucose which end up being secreted in the urine.
