Physiology Flashcards
What is the definition of osmolarity?
Concentration of osmotically active particles present in a solution
Why is the unit of osmolarity usually mosmol/l for body fluids?
They are weak salt solutions
How is osmolarity calcluated?
molar concentration of the solution X no. of osmotically active particles present
What is the normal osmolarity of body fluids?
300 mosmol/L
What is the difference between osmolarity and osmolality?
OsmolaLity has units of osmol/kg water
OsmolaRity has units of osmol/l
virtually they are interchangeable
What is tonicity?
the effect a solution has on cell volume
What is meant by an isotonic solution?
Has no effect on cell volume
What effect does a hypotonic solution have on cell volume?
Increases cell volume
What effect does a hypertonic solution have on cell volume?
Decreases cell volume
What can occur in red blood cells if they are placed in a hypotonic solution?
Cell lysis
they burst
How do urea and sucrose have the same osmolarity, yet urea is a hypotonic solution?
red blood cell membrane is more permeable to urea than sucrose
tonicity takes membrane permeability to substances into account
What is the difference in total body water between males and females?
Males ~60% body weight = water
Females ~50% body weight = water (due to increased fat)
More of the total body water is stored in the extracellular fluid compartment. TRUE/FALSE?
FALSE Intracellular fluid (ICF) 67% of TBW Extracellular fluid (ECF) 33% of TBW
What are the different types of extracellular fluid (ECF)?
Plasma 20%
Interstitial fluid 80%
Lymph
Transcellular fluid (pleural/cerebrospinal)
How do we measure the volume of fluid contained in a body fluid compartment?
We use a tracer and measure the distribution volume
What tracers can be used to measure TBW, ECF and Plasma ?
TBW: 3H2O
ECF: Inulin
Plasma: labelled albumin
Body fluid osmolarity changes when there is a water imbalance (AKA input =/ output). TRUE/FALSE?
TRUE
In what situations would you require extra intake of water due to increased output through sweat and other mechanisms?
In hot weather
During exercise
What ions are plentiful in the ECF?
Na+
Cl-
What ion is mainly foind in the ICF and plays a role in setting a membrane potential?
K+
What is the fluid shift?
Movement of water between ICF and ECF in response to an osmotic gradient.
If the fluid osmolarity is changed, both ICF and ECF volumes will change. TRUE/FALSE?
TRUE
whereas if an isotonic solution is added (e.g. 0.9% saline), only ECF volume will change
Why is low salt intake important in maintaining a healthy blood pressure?
NaCl is isotonic and therefore doesnt change fluid osmolarity
=> only changes the ECF volume (e.g. plasma) => more blood to pump round and heart needs to work harder
Why can minor fluctuations in plasma [K+] have detrimental consequences?
If K+ leaks out of cell and changes the membrane potential this can cause issues in excitable cells
=> Muscle weakness/paralysis
=> cardiac irregularities/arrest
How much salt is excreted in the urine per day (on average)?
10g
What is meant by a functional unit, and what is the functional unit of the kidney?
Smallest structural unit which can perform the function of the organ
=> Nephron
Describe the blood supply to and from the nephron
Artery -> afferent arteriole -> glomerular capillary -> efferent arteriole -> peritubular capillaries -> venule -> Renal Vein
What blood vessels surrounding the nephron are responsible for secretion/ reabsoprtion?
Peritubular capillaries
What is meant by the juxtaglomerular apparatus?
Fork created by the afferent and efferent arteriole
distal convoluted tubule passes through the middle
Tubular fluid changes to what name once it has left collecting duct?
Urine
as it undergoes no further change
What are the two main types of nephron in the kidney?
Cortical (more common)
Juxtamedullary
What differences do juxtamedullary nephrons have compared to cortical nephrons?
Longer loop of henle
NO peritubular capillaries, Instead = vasa rectae
Produce more concentrated urine
Granular cells on the outer membrane of the afferent arteriole produce and secrete what substance?
Renin
What cells are salt sensitive and where are they found?
Macula densa
found in distal convoluted tubule at the juxtaglomerular apparatus
The diameter of the AFFERENT arteriole is larger than that of the EFFERENT arteriole. TRUE/FALSE?
TRUE
Basement membrane is interchangeable with what other term?
Basal lamina
A single layer of capillary endothelial cells and podocytes forms what?
Glomerular Membrane
How much of the plasms which enters the glomerulus from the afferent arteriole is filtered to become tubular fluid?
20%
What are the two calculations which can calculate the rate of excretion?
1) concentration of substance in plasma X GFR
2) concentration of substance in urine X urine production rate (Vu)
If rate of filtration > rate of excretion, has net reabsorption occured?
Yes
If rate of filtration < rate of excretion, then net secretion has occurred
The basement membrane is acellular. TRUE/FALSE?
TRUE
only contains collagen and glycoproteins
A negative basement membrane prevents what?
Large plasma proteins moving from capillary to Bowmans capsule
=> no RBCs in tubular fuid as they cant get through basement membrane
What pressures favour net diffusion into the glomerulus?
glomerular capillary blood pressure
Bowman’s capsule oncotic pressure
What pressures decrease net diffusion into the glomerulus?
Bowman’s capsule hydrostatic pressure
Capillary Oncotic pressure
What is meant by oncotic pressure?
Presence of plasma proteins
How does the glomerular capillary blood pressure remain constant throughout?
Afferent arteriole diameter is larger than efferent arteriole diameter
How is GFR extrinsically regulated?
Sympathetic control via baroreceptor reflex
How is GFR regulated intrinsically?
Myogenic
Tubulogomerular feedback
What is a normal GFR?
around 125 ml/min
Why is Bowmans oncotic pressure normally 0mmHg?
NO plasma proteins can diffuse into the tubular fluid as they are too large
Vasoconstriction decreases GFR. TRUE/FALSE?
TRUE
=> Vasodilation increases GFR
Where are the baroreceptors located?
Arch of Aorta
Carotid sinus
What does Autoregulation prevent?
Small changes in Mean Arterial Blood Pressure changing the GFR
=> helps to maintain unintentional shifts of fluid/salt
Why should the GFR remain constant even at a low BP?
To make sure waste products are still being excreted and not remaining in the body
Describe the process of myogenic autoregulation
vascular smooth muscle is stretched
=>(i.e. arterial pressure is increased
Myogenic makes it contract thus constricting the arteriole to compensate
Describe the process of tubuloglomerular feedback
GFR rises more NaCl flows through tubule Macula densa releases vasoactive chemicals Causes smooth muscle to contract Decreases blood flow to glomerulus
Kidney stones increase what pressure affecting net filtration and GFR?
Bowmans capsule hydrostatic pressure
Due to fluid back up
What can increase capillary oncotic pressure and therefore decrease GFR?
Diarrhoea due to dehydration (loss of water but no loss of plasma proteins)
How is capillary oncotic pressure reduced in patients with severe burns?
The site of the burn loses/leaks plasma proteins
=> decreases Capillary oncotic pressure
=> favours net filtration
=> increases GFR
What is meant by plasma clearance?
volume of plasma completely cleared of a particular substance per minute
What is a normal glucose clearance?
0
(all glucose that is filtered is reabsorbed in the proximal tubule)
=> glucose in the urine is abnormal
How much of the urea that is filtered at the glomerulus is reabsorbed vs excreted in the urine?
50% reabsorbed
50% excreted in the urine
What substance is used to calculate renal plasma flow?
para-amino hippuric acid
What is renal plasma flow?
how much plasma enters the kidneys per minute
What blood vessels secrete PAH into the tubular fluid if it is not filtered at the glomerulus?
secreted from the peritubular capillaries
Where does most reabsorption occur in the nephron?
The proximal tubule
although all parts can reabsorb
What substances are reabsorbed by the kidneys?
99% Fluid and Water
100% Glucose and amino acids
50% Urea
0% Creatinine
How much fluid is reabsorbed into the proximal tubule per minute?
80ml/min
=> if a normal GFR is 125ml/min, then the loop of henle only receives 45ml/min of fluid
What substances are secreted into the proximal tubule?
H+ (maintains acid-base balance) Neurotransmitters (Noradrenaline, Adrenaline, ACh) Drugs (Atropine/Morphine/Penicillin) Bile pigments Uric acid Toxins
What are the 2 ways in which reabsorption can occur?
Transcellular
Paracellular
What membrane of the tubular epithelial cell faces the lumen and which faces the interstitial fluid?
- Apical/luminal membrane faces the Tubular Lumen
- Basolateral membrane faces interstitial fluid
Give an example of Primary active transport and how this works
Na/K Pump
Energy required for this (ATP)
For every ATP = 3 Na+ OUT 2 K+ IN
Describe Secondary Active Transport
The molecule is transported coupled to the concentration gradient of an ion (usually Na+)
Either moves in SAME direction as Na (Symport)
OR in the OPPOSITE direction from Na (Antiport)
What is facilitated diffusion?
Passive carrier-mediated transport of a substance down its concentration gradient
How are Na and Cl reabsorbed from the proximal tubule?
Na = transcellular Cl = paracellular
How are salt and water reabsorbed in equal proportion?
Removing 20% of the plasma fluid in the glomerulus conentrates the plasma proteins in the efferent arteriole/peritubular capillary
This sets up oncotic pressure which drags fluid into the capillary
What transport mechanisms does glucose use at each membrane in order to be reabsorbed into the capillary?
Secondary Active Symport at APICAL membrane
Facilitated Diffusion at Basolateral Membrane
Describe the relationship between plasma glucose level and reabsorption?
Plasma glucose levels can rise until they reach the Transport Maximum
At this level, reabsorption occurs at a steady rate, and glucose which cannot be reabsorbed in time is excreted.
Secreted substances also have a transport maximum (much like reasorbed substances) TRUE/FALSE?
TRUE
e.g. PAH
What is the main function of the Loop of Henle?
Creates a cortico-medullary solute concentration gradient
=>allows formation of hypertonic urine
Describe the difference in water and salt permeability between the descending and ascending limbs of the Loop of Henle?
Descending Limb = impermeable to salt but permeable to water
Ascending Limb = Permeable to NaCl at all points but effectively impermeable to water
How is NaCl reabsorbed in the thick ascending limb?
Into Epithelial cell via triple transporter which also includes K+
Exits epithelial cell via either K/Cl symporter OR Na/K Pump
How does the Loop of Henle change the osmolarity in the tubules and the interstitial fluid?
Solute OUT of ascending limb
=> Osmolarity DOWN
=> Tubular fluid is diluted and
=> OSMOLARITY of interstitial fluid is RAISED
Water leaves the descending limb by osmosis
=> Fluid in the descending limb is concentrated
=> Osmolarity RAISED
What two environments are created when countercurrent multiplication reaches a steady state in the Loop of Henle?
Iso-osmotic going IN
Hypo-Osmotic coming out
What substance passively diffuses into the loop of henle and contributes to the higher osmolarity in the medulla?
Urea
- diffuses into loop
- also adds MORE solute to interstitium
What is the purpose of countercurrent multiplication?
Allows kidney to produce different amounts and concentrations of urine in response to different levels of ADH
What is the normal volume of urine produced with a normal fluid intake?
~1 ml/min
If someone has consumed far more fluid than normal, what can their fluid output rise to?
25 ml/min
What is the countercurrent exchanger in Juxtamedullary nephrons?
Vasa recta
Why are the vasa rectae arranged in hairpin loops?
To counteract the change in osmolarity as they descend into medulla
=> but coming back up the blood that enters the vein has the same osmolarity as blood at start of hairpin
Most filtered ions are reabsorbed before reaching the distal tubule. TRUE/FALSE?
TRUE
What hormones are important in regulating salt and water?
Antidiuretic hormone (ADH) Aldosterone Atrial natriuretic hormone
What is the early distal tubule responsible for reabsorbing?
NaCl
via triple co-transporter (Na/K/2Cl)
What does the late distal tubule reabsorb?
Ca2+
Na+
K+
What is secreted into the late distal tubule?
H+
What type of hormone is ADH and how long is its half life?
OctaPEPTIDE
peptide hormones have relatively short half lives - e.g. 10-15 mins
How is ADH transported from the hypothalamus to the posterior pituitary?
passes down nerve axons
What is the main function of ADH?
Increases permeability of luminal membrane to H2O
by inserting new water channels (aquaporins)
How does ADH let more water into the cells surrounding the lumen?
ADH binds to receptor
Increases intracellular cAMP
Allows aquaporins to set up in apical membrane
Let H2O flow through from tubule/duct
Where are the aquaporins stored when ADH levels are low?
In vesicles in the cell cytoplasm
Describe how more water is reabsorbed when you are dehydrated.
Dehydration = raised plasma osmolarity
Dehydration stimulates MORE ADH
Plasma osmolarity =/ duct osmolarity
=> H2O leaves the duct via aquaporins set up by the ADH
Describe the urine produced when you are dehydrated
Small volume of concentrated urine
as lots of water is reabsorbed
Describe the urine produced when you are over-hydrated and explain why this occurs.
Overhydrated = less ADH release
=> No aquaporins are put into apical membrane for water to move out of the duct and into the cell
=> Large volume of unconcentrated urine
Solute excretion remains the same regardless of ADH. TRUE/FALSE?
TRUE
ADH has no influence over salt excretion
What is the difference between central and nephrogenic Diabetes Insipidus?
Central = can’t make or secrete ADH
Nephrogenic = Can produce/secrete ADH normally, but ADH is not acting on the target cell receptors
What are the main two symptoms of diabetes insipidus?
- Large volumes of dilute urine (up to 20 litres per day)
- Constant thirst
When is aldosterone secreted?
- rising [K+] or falling [Na+] in the blood
- activation of the RAAS system
What is the main function of aldosterone?
Stimulates Na+ reabsorption and K+ secretion
Na+ reabsorption increases BP
Where is most K+ reabsorbed in the kidney?
Proximal Tubule
How are the granular cells stimulated to produce renin?
When the afferent arteriole puts less pressure on the granular cells this produces renin and starts the RAAS pathway
What senses low plasma NaCl levels and encourages the body to reabsorb Na?
Macula densa cells
Aldosterone increases the expression of what ion channels?
Na channels on APICAL membrane
Na/K pump on basolateral membrane
What transporter do loop diuretics inhibit?
Triple cotransporter
Why are heart failure patients treated with diuretics?
Low Cardiac output and BP stimulates fluid retention
BUT this just makes it more difficult for the heart to pump
What is the function of Atrial Naturetic Peptide (ANP)?
Released when heart muscle cells are stretched
DUE TO: increase in the circulating plasma vol.
Promotes excretion of Na+ and diuresis
=> decreasing plasma volume
After what volume has entered the bladder does the micturation reflex occur?
250-400 ml
What is the difference between Water Diuresis and Osmotic Diuresis?
Water diuresis:
- increased urine flow
- NO increased solute excretion
Osmotic diuresis:
- the increased urine flow
DUE TO primary increase in salt excretion
What is the normal blood pH, and is arterial or venous blood usually more acidic?
7.35-7.45
venous blood is usually more acidic due to CO2 forming carbonic acid
Describe the effect acidosis and alkalosis have on the CNS?
Acidosis = depression of the CNS. Alkalosis = overexcitability of the PNS then CNS.
What 3 metabolic actions add H+ to the body fluid?
- Carbonic acid formation
- Inorganic acids produced during breakdown of nutrients
- Organic acids resulting from metabolism
What is the pK of an acid?
The pH it is at when the reaction is at equilibrium
How do the kidneys control HCO3 concentration?
They are able to vary how much is reabsorbed and create more when required
The HCO3 found in the tubule is NOT transported directly to the surrounding tubule cell. TRUE/FALSE?
TRUE
indirectly transported across the membrane via formation and dissociation of carbonic acid
When HCO3 is low in the tubular fluid as it is being reabsorbed, what does the H+ combine with to be buffered?
Phosphate PO4
What transporter does HCO3 use to get from the tubular epithelial cell to the interstitial fluid?
Na/HCO3 co-transporter
When H+ and Phosphate combine this is excreted in the urine. TRUE/FALSE?
TRUE
If all HCO3 and PO4 have been used to buffer H+ yet we are still producing it, what else can be used as the buffer?
Glutamine is broken down to ammonia which can pass into the tubular fluid
This then combines with the secreted H+ to form ammonium ion
This is excreted in the urine
What 3 factors contribute to a normal acid-base balance
Plasma pH (7.4) [HCO3-]p (25 mmol/l) Arterial PCO2 (40 mmHg)
What is meant by compensation of acid base disturbance?
Restore pH to 7.4 as soon as possible
irrespective of what happens to [HCO3-]p and PCO2
What is meant by correction of acid base balance?
Restoring the pH, HCO3- and PCO2 back to normal
What are the 4 main types of acid base disturbance?
Respiratory Acidosis
Respiratory Alkalosis
Metabolic Acidosis
Metabolic Alkalosis
What is meant by “buffering” of a pH change?
Immediate dilution of the acid or base in ECF
Give examples of buffers found in the blood?
Hb
HCO3
What is the disadvantage of buffering?
buffer stores are quickly depleted
=> kidney has to rectify stores
What biochemical abnormality causes respiratory acidosis?
Retention of CO2
What specific conditions can cause respiratory acidosis?
chronic bronchitis chronic emphysema Airway restriction (e.g. asthma/tumour) Chest injuries Respiratory depression (e.g. from morphine)
CO2 + H2O => H2CO3 => H+ + HCO3-
What way does the equilibrium of this reaction shift if a patient is in CO2 retention?
To the right
=> more H+ and HCO3 is made
Describe the appearance of the pH and PCO2 in an uncompensated respiratory acidosis?
pH < 7.35
PCO2 > 45 mmHg
Describe the shift of respiratory acidosis compared to normal on a Davenport diagram?
pH lowers (shifts left) HCO3 conc goes up (shifts up)
There is virtually NO extracellular buffering in respiratory disorders. TRUE/FALSE?
TRUE
How does the renal system compensate for a respiratory acidosis?
high blood PCO2 makes kidney secrete H+ into filtrate
=> H+ is excreted in the urine
All filtered HCO3- is reabsorbed (i.e. no HCO3- excretion)
How is a respiratory acidosis corrected?
Correction requires lowering PCO2 by restoring normal ventilation
What is meant by a respiratory alkalosis?
Excessive removal of CO2 by the body
What actions can cause a respiratory alkalosis?
Low inspired PO2 at altitude
Hyperventilation
Hysterical overbreathing
CO2 + H2O => H2CO3 => H+ + HCO3-
In what direction does respiratory alkalosis cause the equilibrium to move?
To the left due to reduced CO2
This causes a fall in H+ and HCO3- concentration
Describe the appearance of the pH and PCO2 in a respiratory alkalosis?
pH > 7.45
PCO2 < 35 mmHg
Describe the shift of respiratory alkalosis compared to normal on a Davenport diagram?
pH increases (shifts right) HCO3 decreases (shifts down)
How does the kidney compensate a respiratory alkalosis?
Excessive removal of CO2 reduces H+ secretion into the tubule
=> less H+ in the urine
Less HCO3- is reabsorbed => excreted in urine
What causes a metabolic acidosis?
Excess H+ from any source other than CO2
What can cause a metabolic acidosis?
Ingestion of acids or acid-producing foodstuffs
Excessive metabolic production of H+
- lactic acid during exercise
- ketoacidosis in T2DM
Excessive loss of base from the body
- diarrhoea – loss of HCO3-
What happens to the pH and HCO3- in uncompensated metabolic acidosis?
Uncompensated metabolic acidosis indicated by:
pH < 7.35
[HCO3-]p is low
Describe the shift of metabolic acidosis compared to normal on a Davenport diagram?
pH decreases (shifts left) HCO3- decreases (shifts down)
How does the respiratory system compensate in a metabolic acidosis?
Ventilation is quickly increased and more CO2 is blown off
How is metabolic acidosis corrected?
Filtered HCO3- = reabsorbed
H+ secretion produces TA & NH4+
=> generates new HCO3- into blood
Acid excreted in urine
Ventilation can then be normalised
What is a metabolic alkalosis?
Excessive loss of H+ from the body
What actions can cause a metabolic alklalosis?
- Loss of HCl from the stomach (vomiting)
- Ingestion of alkali or alkali-producing foods
- Aldosterone hypersecretion
What indicates an uncompensated metabolic alkalosis?
pH > 7.45
[HCO3-]p is high
Describe the position of a metabolic alkalosis in comparison to normla on a Davenport diagram?
pH increases (shifts right) HCO3 ncreases (shifts up)
How does the respiratory system compensate in a metabolic alkalosis?
Increased pH slows ventilation (peripheral chemoreceptors)
CO2 retained, PCO2 rises
How is metabolic alkalosis corrected?
Not all filtered HCO3- is reabsorbed (due to large vol)
No TA or NH4+ is generated
HCO3- is excreted (urine is alkaline)
[HCO3-]p falls back towards normal
