Physiology Flashcards
What is osmolarity?
Concentration of osmotically active particles present in a solution
What are the units of osmolarity?
osmol/l or mosmol/l
Osmolarity can be calculated if what two factors are known?
- the molar concentration of the solutions
- the number of osmotically active particles present
What is the difference between osmolality and osmolarity?
- osmolality has units of osmol/kg water
- osmolarity has units of osmol/l
What is the effect of isotonic, hypotonic and hypertonic on cell volumes?
- isotonic = no change in cell volume
- hypertonic = decrease in cell volume
What is tonicity?
The effect a solution has on cell volume
Total body water makes up what percentage of body weight in males and females?
- 60% of body weight in males
- 50% of body weight in females
Total body water exists as what 2 major compartments?
- intracellular fluid (67% of TBW)
- extracellular (33% of TBW)
Extracellular fluid includes what?
- plasma
- interstitial fluid
- lymph and transcellular fluid
How can you measure distribution volume of a tracer?
- add a known quantity of tracer X to the body
- measure the equilibrium volume of X in the body
- distribution volume (litres)= Qx (mol) / [X] (mol/litre)
What are the main ions in the ECF?
- Na+
- Cl-
- HCO3-
What are the main ions in the ICF?
- K+
- Mg2+
- negatively charged proteins
The osmotic concentrations of both ECF and ICF are identical - true or false?
True
Define fluid shift
Movement of water between the ICF and ECF in response to an osmotic gradient
Name challenges to fluid homeostasis
- gain or loss in water
- gain or loss of NaCl
- gain or loss of isotonic fluid
Why is electrolyte balance important?
- total electrolyte concentrations can directly affect water balance (via changes in osmolarity)
- the concentrations of individual electrolytes can affect cell function
K+ plays a key role in what?
In establishing membrane potential
Name the functions of the kidneys
- water balance
- salt balance
- maintenance of plasma volume
- maintenance of plasma osmolarity
- acid base balance
- excretion of metabolic waste products
- excretion of exogenous foreign compounds
- secretion of renin
- secretion of erythropoietin
- conversion of vitamin D into active form
What are the functional mechanisms of the nephron?
- filtration
- reabsorption
- secretion
What is the juxtaglomerulus apparatus?
The region of nephron where part of the distal tubule passes between afferent and efferent arteriole, specialised cells important in kidney function
Name the two types of nephron
- juxtamedullary (20%)
- cortical (80%)
What are the differences between the two types of nephron?
In juxtaglomerular nephron;
- loop of henle much longer and descends much further down
- instead of peritubular capillaries it has a single capillary structure (vasa recta)
- responsible for a much more concentrated urine
What makes up the inner layer of the bowmans capsule?
Podocytes
Describe granular cells
- cells that produce and secrete renin
- modified vascular cells
Describe the macula densa
- detects the amount of salt that is present in tubular fluid as it passes through m
- able to signal and release chemical messengers that influence the smooth muscle of the wall of the efferent arterioles
What is urine?
Modified filtrate of the blood
What percentage of the plasma that enters the glomerulus is filtered?
20%
Rate of secretion is equal to ?
rate of filtration + rate of secretion - rate of reabsorption
or
filtration + secretion = reabsorption +excretion
Movements of substances within the kidney are described in terms of what?
Concentration x flow
The rate of filtration of a substance is equal to?
mass of X filtered into the bowmans capsule per unit time
for a freely filterable substance x;
rate of filtration = [x] plasma x GFR
The rate of excretion of a substance is equal to?
mass of x excreted per unit time
[x] urine x Vu (urine production rate)
The rate of reabsorption of a substance is equal to?
rate of filtration of X - rate of excretion of X
The rate of secretion of a substance is equal to?
rate of excretion of X - rate of filtration of X
Rates of reabsorption and secretion reflect what?
- tubular modification of filtrate
- obtained as the difference between filtration and excretion
The fluids filtered from the glomerulus into the bowmans capsule must through what three layers that make up the glomerular membrane?
- lumen of glomerular capillary
- basement membrane
- lumen of bowmans capsule
The basement membrane of the bowmans capsule is composed of what?
- made up of collagen and glycoproteins
- net negative charge
Name the four different forces that comprise net filtration pressure
- glomerular capillary blood pressure (BPGC)
- bowmans capsule hydrostatic (fluid) pressure (HPBC)
- capillary oncotic pressure (COPGC)
- bowmans capsule oncotic pressure (COPBC)
What are starling forces?
The balance of hydrostatic pressure and osmotic forces
What pressures favour the process of filtration?
- glomerular capillary blood pressure
- bowmans capsule oncotic pressure
What pressure oppose the process of filtration?
- bowmans capsule hydrostatic pressure
- capillary oncotic pressure
What is GFR?
The rate at which protein free plasma is filtered from the glomeruli into the bowmans capsule per unit time
What is a ‘normal’ GFR?
125 ml/min
What is the major determinant of GFR?
Glomerular capillary fluid (blood) pressure (BPGC)
How is renal blood flow and glomerular filtration rate regulated?
- extrinsic regulation of GFR; sympathetic control via baroreceptor reflex
- autoregulation of GFR (intrinsic); myogenic mechanism, tubuloglomerular feedback mechanism
Describe the control of GFR by alterations in arterial blood pressure
- fall in blood volume (e.g. haemorrhage)
- decreased arterial blood pressure
- detected by aortic and carotid sinus baroreceptors
- increased sympathetic activity
- generalised arteriolar vasoconstriction
- constriction of afferent arterioles
- decreased BPGC
- decreased GFR
- decreased urine volume (helps to compensate)
Why do changed in systemic arterial blood pressure not necessarily result in changes in GFR?
Autoregulation prevents short term changes in systemic arterial pressure affecting GFR
Describe myogenic autoregulation
If vascular smooth muscle is stretched (i.e. arterial pressure is increased), it contracts thus constricting the arteriole
Describe tubuloglomerular feedback (autoregulation)
- negative feedback
- involves the juxtaglomerular apparatus (mechanism remains unclear)
- if GFR rises, more NaCl flows through the tubule leading to constriction of afferent arterioles
What is plasma clearance?
- a measure of how effectively the kidneys can clean the blood of a substance
- equals the volume of plasma completely cleared of a particular substance per minute
- each substance that is handled by the kidney will have its own specific plasma clearance value
Describe the equation for plasma clearance
clearance of substance X = rate of excretion of X / plasma concentration of X
or
X = [x] urine x V urine / [x] plasma
What is the units for plasma clearance?
ml/min
Measurement of inulin clearance can be used clinically to determine what?
GFR
What can be used instead of inulin clearance?
Creatinine clearance
If clearance
Reabsorbed
If clearance = GFR then the substance is what?
Neither reabsorbed nor secreted
If clearance > GFR then the substance is what?
Secreted into tubule
What is para-amino hippuric acid (PAH)?
An exogenous organic anion
PAH is used to measured what?
To measure renal plasma flow (=650ml/min)
Ideally, any substance used as a clearance marker should have what properties?
- non toxic
- inert (i.e. not metabolised)
- easy to measure
A GFR marker should be?
Filtered freely; not secreted or reabsorbed
A RPF (renal plasma flow) marker should be?
Filtered and completely secreted
What is filtration fraction?
The fraction of plasma flowing through the glomeruli that is filtered into the tubules
What is the equation for filtration fraction?
GFR / renal plasma flow
Reabsorption can occur where?
Along the entire length of the nephron
What is the average GFR?
125ml/min = 180 litres / day
What do the kidneys reabsorb?
- 99% of fluid
- 99% of salt
- 100% of glucose
- 100% of amino acids
- 50% of urea
- 0% creatinine
Is reabsorption specific or non specific?
Specific
compared to filtration which is relatively non specific (based on bulk flow)
What is glomerular filtrate?
A modified filtrate of the blood (i.e. it contains ions and solutes at plasma concentrations but lacks RBCs, large plasma proteins)
The fluid reabsorbed in the proximal tubule is said to be what with the filtrate?
Iso-osmotic
Name substances reabsorbed in the proximal tubule
- sugars
- amino acids
- phosphate
- sulphate
- lactate
Name substances secreted in the proximal tubule
- H+
- hippurates
- neurotransmitters
- bile pigments
- uric acid
- drugs
- toxins
What is the major site of tubular reabsorption within the nephron?
The proximal tubule
Describe the different types of carrier-mediated membrane transport
- primary active transport; energy is directly required to operate the carrier and move the substrate against its concentration gradient
- secondary active transport; the carrier molecule is transported coupled to the concentration gradient of an ion (usually Na+)
- facilitated diffusion; passive carrier mediated transport of a substance down its concentration gradient
What is essential for Na+ reabsorption?
An energy dependent Na+ K ATPase transport mechanism at the basolateral membrane
Where is Na+ reabsorbed?
All regions of the nephron except the descending limb of loop of henle
What drives the reabsorption of Na+?
The presence of basolateral sodium potassium ATPase that drives the reabsorption of sodium from tubular fluid towards the peritubular capillary
Iso-osmotic fluid reabsorption across ‘leaky’ proximal tubule epithelium occurs due to?
- standing osmotic gradient
- oncotic pressure gradient
The net overall movement of sodium ions allows for what?
- Sodium moves into cells and leaves through the basolateral membrane towards the blood
- net movement of positively charged sodium ions towards the blood sets up an electrochemical gradient
- this allow the passive paracellular reabsorption of negatively charged ions (Cl-)
The net movement of glucose from tubular fluid towards the blood will drive what?
The paracellular absorption of H2O
What is the transport maximum?
The maximum rate at which a particular substance can be reabsorbed
What transport systems can become saturated - secretion or reabsorption?
Both
What is the function of the loop of henle?
- generates a cortico-medullary solute concentration gradient
- this enables the formation of hypertonic urine
Describe the fluid flow of the loop of henle
- opposing flow in the two limbs is termed countercurrent flow
- the entire loop functions as a counter-current multiplier
- together the loop and vasa recta establish a hyper-osmotic medullary interstitial fluid
Describe the reabsorption capabilities in the ascending limb of the loop of henle
- along the entire length of the ascending limb Na+ and Cl- are being reabsorbed
- thick (upper) AL this is achieved by active transport and in the thin (lower) AL this is passive
- the ascending limb is relatively impermeable to water
- little or no water follows salt reabsorption
Describe the reabsorption capabilities in the descending loop of henle
- this segment does not reabsorbed NaCl
- highly permeable to water
What enables an osmotic gradient to be established in the medulla?
The selective permeabilities of the ascending and descending limbs of the loop of henle
Loop diuretics block what in the nephron?
The triple co-transporter
K+ recycling in the nephron means what?
The NaCl is absorbed into the interstitial fluid
Describe how the triple co-transporter pumps solute from the thick ascending limb of loop of henle
- solute is removed from lumen of ascending limb (water cannot follow)
- tubular fluid is diluted and osmolality of interstitial fluid is raised
- interstitial solute cannot enter the descending limb
- water leaves the descending by osmosis
- fluid in the descending limb is concentrated
The solute is described as what when leaving the proximal tubule and described as what when entering the distal tubule?
- iso-osmotic leaving the proximal tubule
- hypo-osmotic when entering the distal tubule
What contributes approx. half of the medullary osmolality?
The urea cycle
What is the purpose of the countercurrent multiplication and why?
- To concentrate the medullary interstitial fluid
- to enable the kidney to produce urine of different volume and concentration according to the amounts of circulating antidiuretic hormone
What forms the countercurrent system?
The loop of henle and the vasa recta
Essential blood flow through the medulla tends to wash away NaCl and urea. How is this problem minimised?
- vasa recta capillaries follow hairpin loops
- vasa recta capillaries freely permeable to NaCl and water
- blood flow to vasa recta is low (few juxtamedullary nephrons)
The high medullary osmolarity allows for what?
The production of hypertonic urine in the presence of ADH
What are the major sites for the regulation of ion and water balance?
The distal tubule and the collecting duct
What is the function of ADH?
To decrease urine production by increasing water reabsorption
What is the function of aldosterone?
- increase sodium reabsorption
- increase H+ / K+ secretion
What is the function of atrial natriuretic hormone?
Decrease Na+ reabsorption
What is the function of parathyroid hormone?
- increase Ca2+ reabsorption
- decrease PO4 3-
The distal tubule can be described as two segments - what are they?
Early and late
What occurs in the early segment of the distal tubule?
Na+ K+ 2Cl- transport (NaCl reabsorption)
What occurs in the late segment of the distal tubule?
- Ca2+ reabsorption
- H+ secretion
- Na+ reabsorption (basal state)
- K+ reabsorption (basal state)
The collecting duct can be split into what?
Early and late
Describe the late segment of the collecting duct
- a low ion permeability
- permeability to water (and urea) influenced by ADH
Describe ADH
- octapeptide synthesised by the supraoptic and paraventricular nuclei in the hypothalamus
- transported down nerves to terminals where it is stored in granules in the posterior pituitary
- released into blood when action potentials down the nerves lead to Ca2+ dependent exocytosis
- plasma half life of 10-15 minutes
Describe the effect of ADH on water permeability of the collecting duct
- increases permeability of luminal membrane to H2O by inserting new aquaporins
- ADH binds to type 2 vasopressin receptors on basolateral membrane of cells in collecting duct and distal tubule
- this initiates a cell signalling response; increase of cyclic AMP
- increase in cyclic AMP causes fusion of intracellular vesicle that contains water channels
- these then fuse with the apical membrane and insert aquaporins
- these increase the permebaility of the membrane to water
Describe the movement of water in the presence of
A) maximal [ADH]plasma
B) high [ADH]
C) low [ADH}
A) water moves from the collecting duct lumen along the osmotic gradient into the medullary interstitial fluid thus enabling hypertonic urine formation
B) high water permebaility, hypertonic urine
C) low water permeability, hypotonic urine
Describe diabetes insipidus classification, symptoms and treatment
- classified as central diabetes insipidus, nephrogenic diabetes insipidus
- symptoms include; large volumes of dilute urine (up to 20 litres per day), constant thirst
- treatment; ADH replacement
What is central diabetes insipidus?
Inability to produce or secrete ADH
What is nephrogenic diabetes insipidus?
Some failure of the kidneys to respond to circulating levels of ADH
What is the most important stimulus for ADH release?
Hypothalamic osmoreceptors
Decreased atrial pressures meand that?
Increase ADH release
What is aldosterone?
Steroid hormone secreted by the adrenal cortex
When is aldosterone secreted?
- in response to rising [K+] or falling [Na+] in the blood
- activation of the renin-angiotensin system
What is the role of aldosterone?
- stimulated Na+ reabsorption and K+ secretion
Describe the effects of aldosterone
- normally, 90% o K+ is reabsorbed in the early regions of the nephron (mainly the proximal tubule)
- when aldosterone is absent the rest is reabsorbed in the distal tubule (therefore, no K+ is excreted in the urine)
- an increase in [K+]p directly stimulates the adrenal cortex
- aldosterone stimulates the secretion of K+
- a decrease in plasma [Na+] promotes the indirect secretion of aldosterone by means of the juxtaglomerular apparatus
Describe the control of renin release from granular cells in the juxtaglomerular apparatus
- reduced pressure in afferent arteriole; more renin released, more Na+ reabsorbed, blood volume increased, blood pressure restored
- macula densa cells sense the amount of NaCl in the distal tubule; if NaCl reduced, more renin released, more Na+ reabsorbed
- increased sympathetic activity as a result of reduced arterial blood pressure; granular (renin-secreting) cells directly innervated by sympathetic nervous system, causes renin release
When is ANP released and what are its effects?
- ANP is released when these cells are mechanically stretched due to an increase in the circulating plasma volume
- ANP promotes excretion of Na+ and diuresis, thus decreasing plasma volume
- also exerts effects on the cardiovascular system to lower blood pressure
What is water diuresis?
There is an increased urine flow but not an increased solute excretion
What is osmotic diuresis?
The increased urine flow is as a result of a primary increase in salt excretion
What is the pH of; A) arterial blood B) venous blood C) average pH of blood D) ECF
A) 7.45
B) 7.35
C) 7.40
D) tightly controlled to 7.4
Fluctuations in [H+] can have what effects?
- acidosis can lead to depression of the CNS. alkalosis can lead to overexcitability of the peripheral NS and later the CNS
- [H+] exerts a marked influence of enzyme activity
- changed in [H+] influence K+ levels in the body
H+ is continually added to the body fluids as a result of what?
Metabolic activity
Input must equal output to maintain a constant [H+] in the body fluids
Name the three sources by which H+ is continually added
- carbonic acid formation
- inorganic acids produces during breakdown of nutrients
- organic acids resulting from metabolism
What is the most important physiological buffer system?
The CO2-HCO3 buffer
What is the role of the kidney in control of [HCO3-]?
- variable reabsorption of filtered HCO3-
- kidneys can add ‘new’ HCO3- to the blood
Both of these are dependent upon H+ secretion into the tubule
Describe the formation of ‘new’ HCO3- in the kidneys
When [HCO3-] tubular fluid is low (reabsorption), secreted H+ combines with the next most plentiful buffer in the filtrate, phosphate
What is titratable acid?
- the amount of H+ excreted as (largely) H2PO4-
The vast majority of H+ secretion is used for what?
HCO3- reabsorption to prevent generation of acidosis
