Lecture 52 – Tubular function and hormonal control Flashcards
Electrolyte balance across tubular epithelium
o Na+ is reabsorbed by active transport
o Electrochemical gradient drives anion reabsorption
o Water moves by osmosis, following solute reabsorption
o Concentrations of other solutes increase as fluid volume in lumen decreases. Permeable solutes are reabsorbed by diffusion
Nephron blood supply
Each nephron has two arterioles and two sets of capillaries associated with it
Na+ reabsorbed
o Na+ enters cell through membrane proteins, moving down its electrochemical gradient
o Na+ is pumped out the basolateral side of cell by the Na+-K+-ATPase
Glucose and Na+ reabsorbed
o Na+ moving down its electrochemical gradient using the SFLT protein pulls glucose into the cell against its concentration gradient
o Glucose diffuses out of the basolateral side of the cell using the GLUT protein
o Na+ is pumped out by Na+-K+-ATPase
Filtration rate of glucose vs plasma glucose concentration
Linear proportional positive relationship
Sodium reabsorption
o 80% of oxygen consumed by the kidney
o Tied to reabsorption
Water, chloride
Glucose, amino acids, urea
o Tied to secretion of
Potassium
Hydrogen ions
Sodium reabsorption table
refer to notes
Renin-angiotensin system
o Renin release from granular cells is stimulated by EC volume depletion
Fall in pressure at preglomerular arteriole
Reduction in sodium chloride delivery to macula densa
Sympathetic nerve activation
Sodium balance
o Input
Diet (food and drink) – 150 mmol
Intravenous (normal saline) – 0 mmol
o Output
Urine – 140 mmol
Faeces – 8 mmol
Skin – 2mmol
water balance
o Input
Diet (food and drink) – 2200 mL
Metabolism 300mL
Intravenous (5% dextrose) 0 mL
o Output
Urine 1500 mL
Lungs 500 mL
Skin 400 mL
Faeces 100mL
Detecting changes in osmolarity
o osmoreceptor cells
Anterior hypothalamus
Response to changes in cell size
Vasopressin and osmolarity
Linear proportional relationship that hits a plateau
Vasopressin and ECF volume
Negative linear relationship
Water and the nephron
o Proximal tubule
Bulk absorption
o Descending limb of loop of Henle
Dilution of filtrate
o Collecting ducts
Fine-tuning according to needs
Urine osmolality
o Ranges from 3-1200 mOsM/kgH2O
o Must excrete 600 mOsM of solute per day
o Must excrete at least 500mL of water per day
Concentration of urine along the nephron
o Isosmotic fluid leaving the proximal tubule becomes progressively more concentrated in. the descending limb
o Removal of solute in the thick ascending limb creates hypoosmotic fluid
o Hormones control distal nephron permeability to water and solutes
o Urine osmolarity depends on reabsorption in the collecting duct
Vasopressin binds to membrane receptor
o Receptor activates cAMP second messenger system
o Cell inserts AQP2 water pores into apical membrane
o Water is absorbed by osmosis into the blood
Concentrated urine
With maximal vasopressin, the collecting duct is freely permeable to water. Water leaves by osmosis and is carried away by the base recta capillaries
Dilute urine
In the absence of vasopressin, the collecting duct is impermeable to water and the urine is dilute.
Movement of water across collecting duct lumen to medullary interstitial fluid to vasa recta (blood)
o Vasopressin binds to membrane receptor
o Receptor activates cAMP second messenger system
o Cell inserts AQP2 water pores into apical membrane
o Water is absorbed by osmosis into the blood
Is reabsorption of secretion a bigger tubular activity?
reabsorption
Where is reabsorption greatest along the nephron?
proximal tube
What is the most important solute to be reabsorbed?
sodium
Which solutes are actively reabsorbed?
Sodium, amino acids, glucose, lactate
Glucose appears in the diabetic’s urine because diabetes?
o Because there is an upper limit of glucose that the tubules can reabsorb
o Tm = maximal absorption of substrate
In healthy individuals’ glucose is typically filtered…
o In equimolar amounts found in plasma
o Glucose is not found in healthy individuals excreted urine
o Glucose and amino acid reabsorption is driven by secondary active transport
o Glucose transporters are saturable
o Glucose and amino acids are typically reabsorbed in the PACT
Sodium reabsorption
o In the proximal convoluted tubule, H+ secretion occurs in exchange for Na+ reabsorption.
o H+/proton/hydrogen ion/hydrogen cation secretion in the proximal nephron is functionally due to the need to reabsorb HCO3-/bicarbonate.
o In the distal nephron H+ secretion is intended to regulate acid/base (pH) balance.
Renin-angiotensin-aldosterone system
o The renin-angiotensin-aldosterone system (RAAS) is an endocrine/hormone regulatory system that is essential for the long-term regulation of blood pressure and fluid balance.
o Renin is an endocrine hormone released by the kidneys. Renin acts as an enzyme that catalyses the conversion of angiotensinogen to angiotensin 1.
o Angiotensinogen is produced and secreted from the liver. Angiotensin 1 (Ang 1) is then cleaved to form Ang/angiotensin II by the hormone angiotensin converting enzyme (ACE).
o ACE is synthesised in endothelial cells that line blood vessels. The high density of capillaries in the lungs means that the lungs are a major site of ANG II production.
o The name “angiotensin” indicates that ANG II is a potent vasoconstrictor. ANG II also stimulates aldosterone release from the adrenal cortex.
o Aldosterone/aldosterone promotes sodium reabsorption (in exchange for potassium secretion).
Juxtaglomerular apparatus
o Macula densa cells detect Na+/sodium/Na content in ascending limb of the loop of Henle.
o During tubular glomerular feedback macula densa cell signal to smooth muscle cells on the afferent arteriole to constrict - restricting blood flow to the glomerular capillaries.
o However, if Na+/sodium/Na content in the ascending limb of the loop of Henle is low - suggesting excess water loss - the macula densa cells signal the release of renin from the granular cells.
o High water loss suggests low blood volume and a fall in mean arterial pressure. The pressor effects of Ang II/angiotensin II increases resistance, thus increasing MAP.
Renal sodium excretion can be altered by what?
o Renin-angiotensin system
o Sympathetic nervous system
o Atrial natriuretic peptide
The body detects sodium balance through
o Carotid baroreceptors
o Renal arterial pressure receptors
o Cardia atrial baroreceptors
Infusion of 1L of normal saline will cause a change in blood volume of:
0.25L
Tubular fluid leaving the loop of Henle is normally
dilute
The medullary concentration gradient is mostly the result of
sodium and urea
What things are needed to produce concentrated urine?
o Na/K/2Cl co-transporter
o Aquaporin 2
o cAMP
a negative water balance will be most obvious as
o through changes in osmolarity
o using osmoreceptor cells
a negative water balance will normally result in
o thirst and concentrated urine
o i.e. waking up in morning after not having water overnight
what things are needed to produce concentrated urine
vasopressin (ADH)
