Physiology (1-5) Flashcards
What is osmolarity?
Concentration of osmotically active particles in a solution
What is the approximate osmolarity of the body’s fluids?
~300mosmol/L
How can the osmolarity of a solution be calculated?
If the following are known:
- Molar concentration - Number of particles present
What is the osmolarity of a 100mM solution of magnesium chloride?
Molar concentration = 100mM
Number of particles present = 3
Osmorality = 100 x 3 = 300mosmol/L
What are the units of osmolality?
osmol/kg of water
When are osmolarity and osmolality bascially interchangeable?
Weak solutions
Body fluids
What is tonicity?
Effect a solution has on cell volume
What effect does a hypotonic solution have on cells?
Cell lysis
What effect does a hypertonic solution have on cells?
Cell shrinkage
What does tonicity take into account?
Solute’s ability to cross cell membranes
How much of the total body water is made up of ICF?
67%
How much of the total body water is made up of ECF?
33%
What forms the ECF?
Plasma (20%)
ISF (80%)
Lympha and transcellular fliud (Negligible)
What tracer can we use to calculate total body water?
³H₂O
What tracer can we use to calculate ECF?
Inulin
What tracer can we use to calculate plasma volume?
Labelled albumin
How can we calculate ICF?
TBW = ECF + ICF
We know TBW and ECF from ³H₂O and Inulin respectively
How can we calculate the volume of distribution?
- Add a does of tracer (D) to an unknown volume of water (V)
- Allow tracer to mix evenly
- Take a small sample and measure [Tracer] (C)
- Calculate V as follows:
V(litres) = Does (D)/Sample
Where [Sample] = Mass/Volume in mg/L
Calculate the volume of distribution for the following values:
- Dose given = 42mg
- Sample volume is 5ml
- Sample tracer mass is 0.01mg
[Tracer] in sample = 0.01/0.005 = 2mg/L
V = 42/2 = 21L
Which of the following are sensible water losses and which are insensible:
- Sweat
- Faeces
- Skin
- Urine
- Lungs
Sensible: - Sweat - Faeces - Urine Insensible: - Skin - Lungs
What sources of water loss are increased and decreased in hot weather?
Increased: - Sweat Decreased: - Lungs - Urine
What sources of water loss are increased and decreased during prolonged heavy exercise?
Increased: - Lungs - Sweat Decreased: - Urine
What is the main method of maintaining water balance?
Increasing water intake
What is the ionic composition of ICF in regards to the following ions:
- Na+
- K+
- Cl-
- Bicarbonate
Sodium -> 10mM
Potassium -> 140mM
Cloride -> 7mM
Bicarbonate -> 10mM
What is the ionic composition of ECF in regards to the following ions:
- Na+
- K+
- Cl-
- Bicarbonate
Sodium -> 140mM
Potassium -> 4.5mM
Cloride -> 115mM
Bicarbonate -> 28mM
What are the main ions in the ICF?
Na+
Cl-
Bicarbonate
What are the main ions in the ICF?
K+
Mg²⁺
Negatively charged proteins
What causes water movement between the ICF and ECF?
Osmotic gradient
What results when there is a gain or loss of H₂O in regards to fluid osmolarity and ICF/ECF volumes?
Change in fluid osmolarity
Similar change in ICF and ECF volumes
What results when there is a gain or loss of NaCl in regards to fluid osmolarity and ICF/ECF volumes?
Change in fluid osmolarity Increased ECF NaCl: - Increased ECF volume - Decreased ICF volume Decreased ECF NaCl: - Decreased ECF volume - Increased ICF volume
What results when there is a gain or loss of isotonic fluid in regards to fluid osmolarity and ICF/ECF volumes?
No change in osmolarity
Change in ECF volume
What does the kidney alter in terms of the ECF and what is this vital for?
Composition
Volume:
- Both aid in BP control
What affect can small leaks or increased cell uptake of K⁺ have?
Severe changes in [K⁺]p:
- Muscle weakness -> Paralysis - Arrhythmias -> Cardiac arrest
What does the rate of excretion of any substance equal?
Filtration rate + Secretion rate - Reabsorption rate
What does the rate of filtration of a substance X equal?
[X]plasma x GFR
What does the rate of excretion of a substance X equal?
[X]urine x Vu (urine flow rate)
What does the rate of reabsorption of a substance X equal?
Rate of Filtration of X - Rate of Excretion of X
What does the rate of secretion of a substance X equal?
Rate of Excretion of X - Rate of Filtration of X
If there is net reabsorption of a substance, what must be true?
Rate of Filtration > Rate of Excretion
If there is net secretion of a substance, what must be true?
Rate of Filtration
What acts as a barrier to RBC filtration into the glomerulus?
Glomerular capillary endothelial cells
What acts as a barrier to plasma protein filtration into the glomerulus?
Basement membrane
Slit processes of podocytes in glomerular epithelium
What is the approximate glomerular capillary BP/hydrostatic pressure (BPgc)?
55mmHg
What is the approximate Bowman’s capsule hydrostatic pressure (Hpbc)?
15mmHg
What is the approximate capillary oncotic pressure (COPgc)?
30mmHg
What is the approximate Bowman’s capsule oncotic pressure (COPbc)?
0mmHg
How can the net filtration pressure be calculated?
(BPgc + COPbc) - ( Hpbc + COPgc)
(55 + 0) - (15 + 30) = 10mmHg
What is the balance of hydrostatic pressure and osmotic forces known as?
Starling forces
How can GFR be calculated?
Filtration coefficient (Kf) x Net filtration pressure
What is the filtration coefficient?
How ‘hole-y’ the glomerular membrane is
What is a normal GFR?
Approximately 125ml/min
What is the main determinate of the GFR?
Glomerular afferent capillary BP/hydrostatic pressure
How are renal blood flow and GFR maintained extrinsically?
Sympathetic control -> The baroreceptor reflex
How are renal blood flow and GFR maintained intrinsically?
Myogenic mechanism
Tubuloglomerular feedback
What happens to BPgc if the afferent arteriole is:
- Constricted
- Dilated
Constricted -> Falls
Dilated -> Rises
What does autoregulation of renal blood flow do?
Prevents short-term BP changes affecting the GFR
How does the myogenic mechanism aid autoregulation of renal blood flow?
If vascular smooth muscle is stretched (due to increased BP) it contracts -> Afferent arteriole constriction -> GFR reduced
How does Tubuloglomerular feedback aid autoregulation of renal blood flow?
Involves the justaglomerular apparatus:
- If GFR rises -> Tubular NaCl flow increases - > Afferent arteriole constriction -> GFR reduced
What can cause an increased Bowman’s capsule hydrostatic pressure and what effect does this have on GFR?
Kidney stone
Reduces GFR
What can cause an increased glomerular capillary oncotic pressure and what effect does this have on GFR?
Diarrhoea
Reduces GCR
What can cause a decreased glomerular capillary oncotic pressure and what effect does this have on GFR?
Severe burns
Increased GFR
If the filtration coefficient is reduced, what happens to GFR?
Decreases
What is plasma clearance?
Volume of plasma completely cleared of a substance per minute (ml/min)
How can we calculate the clearance of substance X?
Clearance of X = Rate of Excretion of X / [X]p
Clearance of X = [X]u x Vu / [X]p
What is the clearance of a substance which is filtered, completely reabsorbed and not secreted? Give an example?
Zero
Glucose
When else is the clearance of a substance 0?
If substance is not filtered and not secreted
What is the clearance of a substance which is filtered, partly reabsorbed and not secreted? Give an example?
Clearance
What is the clearance of a substance which is filtered, secreted and not reabsorbed? Give an example?
Clearance > GFR
All of filtered plasma cleared
Peritubular plasma also cleared
H+
If clearance
Substance is reabsorbed
If clearance = GFR?
Substance neither reabsorbed or secreted
If clearance
Substance secreted
What can Para-amino Hippuric Acid (PAH) be used to calculate?
Renal plasma flow
What is a normal renal plasma flow?
650ml/min
WHich of the following is not a feature of PAH:
- Freely filtered at glomerulus
- Produced in small (but quantifiable) amounts by the body
- Secreted into tubule
- Not reabsorbed at all
- Completely cleared from plasma
Produced in small (but quantifiable) amounts by the body
True or False; All PAH which escapes filtration is secreted from peritubular capillaries?
True
What is the filtration fraction?
Fraction of plasma flowing through glomeruli which is filtered into tubules
What properties should a clearance marker have?
Non-toxic
Inert (not metabolised)
Easy to measure
What additional features should a GFR marker have?
Freely filtered
Not:
- Secreted
- Reabsorbed
What additional features should a RPF marker have?
Freely filtered
AND
Completely secreted
Why is inulin not a convenient substance to use to estimate GFR?
Requires a constant infusion to maintain [Inulin]p
How is the filtration fraction calculated?
GFR/Renal Plasma Flow
What is the normal filtration fraction?
~20%
How is renal blood flow calculated?
RPF x 1/1-HCT (Where HCT is the Haematocrit):
- HCT is the % of blood which is RBCs
-> ~45% in males
-> ~40% in females
RBF = 650/1-0.45 = 650 x 1.85 = 1200ml/min
What rate is the filtrate absorbed in the PCT?
~80ml/min
What rate is the filtrate absorbed in the Loop of Henle?
~45ml/min
Is reabsorbed fluid hypotonic, isotonic or hypertonic to the glomerular filtrate?
Isotonic
Which of the following is not reabsorbed in the PCT:
- Sugars
- Amino acids
- Na⁺
- PO₄³⁻
- SO₄²⁻
- Lactate
Na⁺
Which of the following is not secreted into the PCT:
- H⁺
- Hippurates
- Neurotransmitters
- Bile pigments
- K⁺
- Uric acid
- Drugs
- Toxins
K⁺
What are the two routes by which a substance can be reabsorbed from the tubule?
Transcellular (mainly)
Paracellular
How does primary active transport work?
Energy required to operate carrier
Substance moved AGAINST its concentration gradient
How does secondary active transport work?
Carrier molecule transported coupled to the concentration gradient of an ion -> Usually Na⁺
How does facilitated diffusion work?
Passive carrier-mediated transport
DOWN its concentration gradient
What chemicals can diffuse through the lipid bilayer?
Oxygen and Carbon dioxide
Give an example of a compound that is carried through a membrane by facilitated diffusion?
Glucose
Give an example of a primary active transport
Na+/K+ ATPase:
- Na+ reabsorbed - K+ secreted
Give an example of secondary active transport
Na+/Glucose co-transporter:
- Glucose carried coupled to Na+
What is the approximate renal threshold for glucose?
[Glucose]p 10-12mmol/L
What is the transport maximum for glucose?
~2.0mmol/min
What happens once glucose filtered > glucose reabsorbed?
Excretion = Filtration = Reabsorption
What happens to the clearance of a substance that is reabsorbed or secreted once Tm (Transport maximum) is reached?
It is not constant
How is Cl- reabsorption driven in the PCT?
Na+ reabsorption drives Cl- reabsorption via the paracellular pathway
How is water reabsorbed in the PCT?
Osmosis
What is the osmolality of the tubular fluid when it leaves the PCT?
~300mosmol/L (ie isotonic to plasma)
What are the main functions of the Loop of Henle?
Generates a corticomedullary solute concentration gradient
Helps form hypertonic urine
What sort of flow does the Loop of Henle have?
Countercurrent
What runs alongside the Loop of Henle that helps establish a hyperosmotic medullary ISF?
Vasa recta
What is reabrosbed in the ascending limb of the Loop of Henle?
Na+ and Cl-
How does reabsorption occur in the thick upper part of the ascending limb of the Loop of Henle?
Active transport
How does reabsorption occur in the thin lower part of the ascending limb of the Loop of Henle?
Passive transport
How permeable is the ascending limb of the Loop of Henle to water?
Very impermeable (little/no water follows Na+)
What processes do and don’t occur in the descending limb of the Loop of Henle?
Highly permeable to water -> Reabsorbed
NaCl is NOT reabsorbed
What transporter is present on the apical/lumenal membrane of the PCT?
Na+/K+/2Cl- co-transporter
What transporters are present on the basolateral membrane of the PCT?
K+/Cl- co-transported
Na+/K+ exchanger
What does K+ recycling in the PCT do?
Allows NaCl to be absorbed into the ISF
The following steps are the first part in setting up the corticomedullary solute concentration gradient via the triple co-transporter, put them in order:
- ISF can’t enter DL of Loop of Henle
- Fluid in DL is concentraed
- Tubular fluid diluted and ISF osmolarity rised
- NaCl removed from AL (and water can’t follow)
- Water leaves DL by osmosis
- NaCl removed from AL (and water can’t follow)
- Tubular fluid diluted and ISF osmolarity rised
- ISF can’t enter DL of Loop of Henle
- Water leaves DL by osmosis
- Fluid in DL is concentraed
After the initial corticomedullary solute concentration gradient via the triple co-transporter is set up, what happens next?
- Fluid enters descending limb of Loop of Henle
- Fluid moves into ascending limb
- Hypotonic fluid enters DCT
What is the third step in setting up the corticomedullary solute concentration gradient?
- Solute pumped out of ascending limb
- ISF osmolarity rises
- Passive water efflux from descending limb
- Flow occurs
How does countercurrent multiplication finish the set-up of the corticomedullary solute concentration gradient?
- Iso-osmotic fluid leaves the PCT and enters the descending limb of the Loop of Henle
- Hypo-osmotic fluid enters the DCT
- Horizontal gradient multiplied into a large vertical gradient
What are the steps in the urea cycle throughout the nephron?
- PCT and Loop of Henle relatively impermeable to urea -> Concentration in tubule rises
- DCT is totally impermeable to urea -> [Urea]t rises
- ~50% of urea absorbed into ISF at the collecting duct
- Urea diffuses passively into Loop of Henle
Why is a corticomedullary solute concentration gradient set up?
Enables the kidnesy to produce urine of varying volumes and concentrations
What is the Vurine on normal fluid intake?
~1ml/min
Which nephrons does the vasa recta run alongside?
Juxtamedullary nephrons
What happens to the blood in the vasa recta?
Equilibrates with ISF due to the ‘leaky’ endothelium
What happens to the blood osmolarity as the vasa recta enters the medulla?
It increases:
- Water leaves - Solute enters
What happens to the blood osmolarity as the vasa recta rises back into the cortex?
It decreases:
- Water enters - Solute leaves
The vasa recta blood flow tends to wash away the concentration gradient set up in the medulla, how is this reduced?
- Vasa recta follows hairpin turns
- It is freely permeable to NaCl, water and urea
- Vasa recta blood flow is low