renal 7-10 Flashcards
What is the normal range of plasma osmolality?
- 280-290 mosmol/Kg H₂O (± 3)
- (max. urine osmolality is 1400 mosmol/kg H₂O)
What is ADH, where is it produced and what is its half-life?
- nonapeptide synthesised in supraoptic and paraventricular nuclei (SON and PVN) located in the hypothalamus
- t½ of 15 mins (degraded in liver and kidney)
What does ADH (8-arginine-vasopressin) do and what does this make it?
- increases H₂O permeability of cortical and medullary collecting ducts
- concentrates urine → anti-diuretic
What is diuresis?
Hint - the opposite of anti-diuresis
increased production of urine
What happens to urine with and without ADH?
- w/o ADH, more dilute urine produced
- w/ ADH, less conc. urine produced
What is ADH synthesised within?
Hint - look at the bigger inactive picture
a large precursor molecule (166 AA) → molecule:
[Leader-ADH]-gly-lys-arg-[neurphysin]-arg [Glycopeptide (copeptin)]
To which two locations does ADH move into after its synthesis?
(Hint - S/P → n (pp) → a of hthp tract)
SON/PVN → neurohypophysis (posterior pituitary) → axons of hypothalamohypophyseal tract
What happens to ADH during movement, where is it stored and why?
(Hint - stored in neuro-thing)
- progressively cleaved
- within neurophysin (protein) in nerve terminals
- released into bloodstream when required
What is the primary stimulus for ADH and what is it detected by?
- primary stimulus is change in plasma osmolality
- sensed by osmoreceptors
What are osmoreceptors and what is their threshold for activation?
- a collection of cells located near SON
- threshold for activation 280 mosmol/kg H₂O → small amount of tonic ADH release and linear response if plasma osmolality rises
What type of system is the ADH system and how can this threshold be reset?
- very sensitive system
- reset by other factors i.e. hypovolaemia: hypo-(= low)-vol-(= volume)-emia(= of blood)
State five factors other than plasma osmolality stimuli for ADH release.
(Hint - BP/volume, sickness, BGC, oxygen, tension)
- haemodynamics (BP/volume via baroreceptors) → less sensitive (10-15% change required) but response exponential → hence, drugs affecting BP also affect plasma ADH levels
- nausea → instant and profound body trying to preserve water, plasma ADH increases 100-1000-fold
- hypoglycaemia (modest changes)
- hypoxia (via carotid chemoreceptors)
- angiotensin (increased osmotic response)
What is the mechanism for ADH action? Use the diagram in the notes.
(Hint - ADH via AC via GPs → cA → PKA → A-2 water channels → insert into upper membrane → more water can pass → more water kept → more salty urine)
- principal cells have V₂ receptors on basal membrane for ADH
- ADH activates adenylate cyclase (via G-proteins) → produce cAMP → activates protein kinase A (PKA) → PKA phosphorylates non-functional aquaporin-2 water channels → these channels insert into apical membrane → water permeability increases → water reabsorption → urine concentrates
What does the volume of urine (of a certain concentration) excreted depend on?
(Hint - ADH + n of solute)
- concentrating ability of kidney limited therefore, volume of urine excreted depends on:
• level of circulating ADH
• amount of solute to be excreted
What is the minimum volume of urine which can be excreted?
Hint - a digit of 4 divided by a digit of 7
800/1400 kg H₂O/24 h = 0.571L/24h
If the amount of solute to be excreted in a urine sample is 2000 mosmol/kg H₂O, calculate the min. volume of urine to be excreted to achieve this.
(Hint - where the min. volume of urine which can be excreted is 1400)
2000/1400 = 1.4L
What would happen to the hydration status of a man who drank 1L of 2000 mosmol/kg H₂O solution?
(Hint - would be a loss/gain, miliosmoles + what would be needed?)
- solution of high osmolality would mean gaining a L of fluid
- 2000 milliosmoles = more water would need to be used
Describe the pelvic nerve micturition reflex including the roles of stretch receptors.
(Hint - v of urine → pressure → s. receptors of bladder + pelvic nerve A → pelvic nerve E + IU sphincter → urine urge sent to brain)
volume of urine increases → pressure rises → stretch receptors in bladder activate pelvic nerve afferents → pelvic nerve efferents relax internal urethral sphincter → urge to urinate communicated to higher centres (pons)
(NB: rugae unfold as bladder initially fills so little pressure change)
How does voluntary control in the pelvic nerve micturition reflex occur?
(Hint - done using pons too, pud nerves involved keeping EUS closed, pud nerve activation allows EUS relaxation + urine flow)
- achieved by integration with (pons) via pudendal nerves
- pudendal nerves tonically active → keep external urethral sphincter closed
- voluntary inhibition of pudendal nerve activity relaxes external sphincter allowing micturition
State the events that occur when we deviate from normal osmolality (285mosmol/kg H₂O) due to:
a) water deprivation, solute ingestion, diarrhoea
b) excess fluid digestion
(Hint - effect on ECF osmolality → ADH response towards hypothalamic receptors → CD water permeability → water retention/excretion by kidneys, lateral preop nuclei → thirst and water intake/excretion - NB: ECF osmolality is the reverse of what you think would happen in each situation)
a) increased ECF osmolality, so hypothalamic receptors (supraoptic + paraventricular nuclei):
- ADH release from posterior pituitary → collecting ducts water-permeable → water retention by kidneys → returns to normal (min urine volume 300ml/day)
• lateral preoptic nuclei → thirst → water ingestion → returns to normal
b) decreased ECF osmolality, hypothalamic receptors (supraoptic and paraventricular nuclei):
- ADH release suppressed → collecting ducts water-impermeable → water excretion by kidneys (max. urine volume approx. 23L/day) → returns to normal
• lateral preoptic nuclei → thirst suppressed
Which two things is water excretion regulated by?
Hint - literally by water levels and salt balance
- ECF osmolality (water and salt content regulation)
- Na⁺ balance (major ECF cation)
What response is caused in the body by increased/decreased Na⁺?
(Hint - excess salt it leads to high BP, too little salt means the volumes and pressures of cells are irregular/low)
- excess Na⁺ is a major factor in hypertension
- decreased Na⁺ levels can lead to hypovolaemia and hypotension
How is Na⁺ content restored when there is increased/decreased ECF Na⁺?
(Hint - effect on osmolality → water needs → return to normal osmo and ECF volume)
- increased ECF Na content e.g. NaCl ingestion → increased osmolality → water retention/thirst → normal osmolality + increased ECF volume
- decreased ECF Na content e.g. sweating with only H₂O being replaced → decreased osmolality → water excretion → normal osmolality + decreased ECF volume
How can the amount of Na⁺ reabsorption be modified?
Hint - about the EC circulation and water changes
by changes in ECF (effective circulating fluid) and ECV (effective circulating volume)
What is ECV and what should it not be confused with?
Hint - ECV is not IVCLR
- the component of blood which is perfusing the tissue
- not the same as intravascular (blood) volume e.g. congestive HF can affect CO affecting ECV values
What is renin?
Hint - not a hormone but an active-siter stored in the kidney jug
an enzyme synthesised and stored in juxtaglomerular apparatus of kidneys
State three stimuli for renin release and what they are all reflective of?
(Hint - (1) symp nerves (2) tension AA (3) Na⁺ delivery → decrease in a volume by a change in salt)
- increased sympathetic nerve activity (baroreceptor reflex)
- decreased wall tension in AA
- decreased Na⁺ delivery to macula densa
- all reflective of a decrease in ECV caused by decreased body Na
By which mechanism does renin release from the macula densa occur and via which receptors are sympathetic nerves affected?
(Hint - PG hormone, granular cells and the main enzyme, and the main receptors of your drug monograph)
• macula densa →
- releases prostaglandin I₂ (PGI₂)
- stimulates granular cells to release renin into blood
- sympathetic nerves via β-adrenoreceptors
What are the actions of renin?
‘angio-(=blood vessels)tensin(=tension/BP)’
(Hint - angiotensinogen → atn I (main enzyme) → atn II from which the main action comes from, also pp into decta into octa)
- (acts on p. protein) angiotensinogen → angiotensin I (decapeptide by enzyme ACE) → angiotensin II
- angiotensin II is the primary hormone in Na⁺ regulation (an octapeptide)
How is angiotensin II broken down and into what?
Hint - by pp enzymes into atn 3 + by-products
- by plasma peptidases into:
- angiotensin III + inactive products
What are the effects of the RAAS on:
a) increased BP (Hint - affects salt affecting AA)
b) decreased kidney Na⁺ (Hint - the whole shebang of the RAAS response)
- decreased Na⁺ → afferent arteriole BP decreased
- → angiotensinogen I → angiotensinogen II → angiotensinogen III (broken down into inactive products)
What does the removal of the adrenal glands cause and why?
Hint - you can’t survive w/o it
metabolic defects → death within two weeks because of adrenal insufficiency due to a disease
What are four main effects would removal of the adrenal glands have on the body?
(Hint - (1) loss of salt from urine, (2) EC salt decreases, (3) ECF lessens, (4) circulation topples over)
- loss of NaCl from body via urine
- extracellular Na⁺ content falls
- ECF volume markedly reduced
- circulatory collapse
How can death due to removal of the adrenal glands be avoided?
(Hint - lots of salt and injecting aldo)
high Na⁺ diet and aldosterone administration
What is aldosterone and where is it synthesised?
Hint - a mineral hormone made from the main chol fat, histology GFR the outside layer of adr. gland
- mineralocorticoid (regulates body salts) synthesised from cholesterol
- secreted by zona glomerulosa of adrenal gland
What are the three stimuli for aldosterone release?
Hint - too little salt, too many bananas, too little water
- decrease in plasma Na⁺ concentration → not an important stimulus under normal conditions
- increase in plasma K⁺ concentration → very sensitive (small change causes lots of release)
- decrease in ECV → via angiotensin II
What effects does aldosterone have on bodily ion concentrations?
(Hint - keeps salt, gets rid of banana, gets rid of lemons, promotes salt return in gut and eccrine glands)
- stimulates Na⁺ reabsorption in collecting duct
- stimulates K⁺ secretion in collecting duct
- stimulates H⁺ secretion in collecting duct
- promotes Na⁺ reabsorption in gut and sweat glands
What effect does aldosterone have on ion transport in:
a) principal cells? (Hint - principally 2 positive ions - salt and bananas)
b) intercalated cells? (Hint - CA leaves and normal lemon enters)
a) Na⁺ IN and K⁺ OUT
b) H⁺ IN and HCO₃⁻ OUT
What is ANP?
Hint - 4x7 long, released from A cells when A stretch, act on names receptors in CD, N → promote Na loss
- 28 AA cardiac hormone (from 126 AA prohormone)
- released from atrial cells in response to atrial stretch (hypervolaemia)
- acts at ANP receptors in collecting duct
- natriuretic (promotes Na⁺ loss in urine)
State the mechanism of ANP action.
(Hint - inhibits the pumper and aldo, reduces the main RAAS enzyme release, promotes vasod increasing kidney function measurement G, also note atrial ‘natriuretic’ peptide so this is also a function)
- inhibits collecting duct Na-K ATPase and aldosterone secretion
- reduces renin release (indirectly inhibits aldosterone release)
- promotes vasodilatation of AA (increases GFR)
- ‘natriuretic’ = decrease in Na reabsorption
What is urodilatin?
Hint - ANP replica with a few extra AAs, a natro from kidneys
- a natriuretic originating in kidney
- almost identical to ANP (+4 AAs) + same actions
What is dopamine?
Hint - a natro from the PT, inhibits two forms of Na pump
- natriuretic synthesised in proximal tubule
- inhibits Na-K ATPase and Na-H antiport
What are kinins?
Hint - natros + dilator proteins, oppose ADH action, produced by the named ‘ogens’
- natriuretic and vasodilator peptides
- counteract ADH
- produced from kininogens (by enzyme kallikrein)
What is adrenomedullin?
Hint - a kidney peptide made of 5-2 diet AAs, affects main measure of kidney function, ‘natro’
- 52 AA peptide synthesised in kidney
- increases GFR
- natriuretic → decreases Na⁺ tubular reabsorption
What do hormones ANP, VNP, aldosterone and the RAAS do in combination?
(Hint - all to do with having enough fluid to supply tissues)
encourage retention of water etc to maintain tissue perfusion
What is erythropoiesis and what is the role of EPO in this?
- the production of RBCs in bone marrow stimulated by glycoprotein erythropoietin (EPO):
- made of 166AAs and stimulates erythropoiesis
- 80% produced in kidney (some in liver) by mesangial cells and tubule cells
What are the stages of the negative feedback loop for erythropoiesis?
(Hint - less oxygen → messenger/tube cells → blood fluid EPO levels → stem cells in BM → pro-blasts → RBCs)
plasma hypoxia (by cortical prostaglandins) → mesangial/tubular cells → plasma EPO → BM stem cells → proerythroblasts → erythrocytes → (return to normal)
What happens to EPO in the case of renal failure and how can this be solved?
(Hint - which common condition is less EPO associated with, same way insulin is given but more pricey)
- less EPO produced → patients develop anaemia
- synthetic EPO available but costly
Why is tight regulation of calcium ions necessary?
crucial for proper functioning of excitable cells
In which two forms is Ca2⁺ present in plasma and at what concentration?
(Hint - in jail or a free ion)
- ionised (free) Ca2⁺ ions
- bound Ca2⁺ (to proteins and organic acids)
- more physiologically important when ionised
- both at 1.25 mM
- total plasma measurement = 2.5 mM (double 1.25 mM)
- i.e. ISF Ca2⁺ only 1.25 mM (activity)
Why is ISF Ca2⁺ lower than total plasma Ca2⁺?
Hint - bound/free issue
- because Ca2⁺ ions near interstitial fluid are membrane-bound
- but in plasma there are more free Ca2⁺ ions
In ICF, ionised (free) Ca2⁺ is only 0.0001mM. Why?
Hint - calcium synthesizes vitamin D
used up when synthesising calcium/vitamin D by cells
How can exchangeable Ca2⁺ be lost from bone/ECF/ICF?
Hint - ureters, sphincters, breastmilk or birthing
- faeces
- urine
- pregnancy/lactation
How does the proportional tubular handling of calcium occur?
Hint - half is bound to alby and 1/20th is excreted, the rest is taken back in by proximal tube
- 50% of plasma Ca2⁺ bound to albumin
- 5% filterable so appears in urine while rest is reabsorbed in PCT
How is Ca2⁺ reabsorbed in the PCT and what happens to its concentration along the CT?
(Hint - parallels Na⁺ and H₂O → over 1/2 calcium taken back in, scientists don’t know the mechanism but they guess it is one of the two Ca pumps involved)
- 60% of fluid Ca2⁺ passively reabsorbed by peritubular (basolateral) transport
- mechanism not fully determined, possibly:
•Ca-ATPase
•Ca/Na antiport – (3Na⁺ for 1 Ca2⁺)
How is Ca2⁺ reabsorbed along the loop of Henle, the distal tubules and collecting duct?
(Hint - in LoH almost 1/4, in DT and CD 1/20 or 1/10 taken back in but actively this time)
- loop of Henle → 20-25% of fluid of Ca2⁺ passively reabsorbed in TAL
- distal tubule and CD → 5-10% of fluid of Ca2⁺ actively reabsorbed
- active (must go against conc. gradient, ATP required)
How is calcium reabsorption regulated in a nephron?
Hint - by PTH in the named gland
by parathyroid hormone in the parathyroid gland (4 parts → L superior PTG, R superior PTG, L inferior PTG, R inferior PTG)
What is parathyroid hormone?
Hint - 21x4, synthesised in the instruction cells of PTH glands, released when you need Ca2⁺
- polypeptide (84 AAs)
- synthesised in principal cells of parathyroid glands
- released to stimuli of decreased plasma Ca2⁺
- main function = to increase plasma Ca2⁺
What are the three actions of parathyroid hormone?
Hint - from bone, via vit D indirect, via calcitr hormone
raises plasma Ca2⁺ by:
1) directly liberating Ca2⁺ from bone by matrix breakdown: increasing osteoclast numbers + activity for reabsorption
2) indirectly decreasing Ca2⁺ excretion via vitamin D
3) calcitriol effects:
- decreased Ca2⁺ excretion
- indirect PTH effects → increase of intestinal Ca2⁺ absorption
What is vitamin D3?
Hint - made from cholesterol and by PF cells, active form of c, opposes PTH
- steroid peptide hormone synthesised in parafollicular cells of thyroid gland
- active form of calcitriol (1,25-dihydroxycholecalciferol)
- functionally antagonises PTH actions → promotes laying down of bone
What are the three stages of gaining active vitamin D3 from the diet and sun?
(Hint - diet + skin (7) → cholecalciferol, vit hepatically → 25 circulating form, converted renally → calcitrol 125, the main man)
diet + skin (7-dehydrocholecalciferol) via UV light → cholecalciferol, vitamin D3 (to liver) → 25-hydroycholecalciferol, circulating form (kidney - conversion by PTH) → calcitrol - active form (1,25-dihydroycholecalciferol)
Which organ does:
a) PTH affect?
b) calcitrol affect?
and what happens once Ca2⁺ levels return to normal?
(Hint - BI)
a) bone
b) intestine
- PTH levels decrease
A lack of which two molecules can lead to osteoporosis?
vitamin D and calcitonin
What is rickets and what can it lead to?
basically your bones are all done for → muscles too → don’t grow
- bone pain/tenderness
- skeletal deformities
- increased tendency toward bone fractures
- enlarged joints
- dental deformities
- decreased muscle tone and cramping
- impaired growth and short stature
What is an acid and a base?
- acid: yield protons (H⁺) in solution
- base: accept protons (H⁺) in solution
Compare strong and weak acids/bases.
- strong acids/bases dissociate more in solution than weak ones
- strong acids liberate more protons and weak acids are able to buffer protons
How do we quantify acid dissociation and strength?
- dissociation (below) for given acid is a constant called K
- HA → H⁺ + A-
{acid proton + conjugate base} - for convenience, acid strength quantified by pH scale
- log scale means 1-fold change in pH = 10-fold change in [H+]
What is the normal body [H⁺] and pH in ECF and pH in arterial and venous?
(Hint - same range expect the boundaries and used with arteries more alkaline and veins more acidic)
- [H⁺] is 4 x 10-8 M in ECF
- using equation, average pH is 7.4 (7.35-7.45)
- arterial blood pH = around 7.45
- venous blood pH = around 7.35
What pH range is compatible with life and what occurs outside of these values?
- pH range compatible with life = 6.8 to 8.0
- death rapidly occurs outside these values
- acidosis = >7.35
- alkalosis = <7.45
Which three main significant effects can small changes in pH have?
(Hint - nerves, enzymes and potassium balance)
- nerve excitability
- acidosis = decreased CNS activity (disorientation, coma, death)
- alkalosis = increased CNS activity (pins/needles, muscle twitch, death) - enzyme activity
- made of AAs which have titratable side-chains (R-groups)
- R-group charge vital to correct folding
- 3D shape of enzymes vital to functioning - K⁺ homeostasis
- proton handling and K⁺ secretion intimately linked
- acidosis: increased secretion of H⁺ results in decreased secretion of K⁺ → hyperkalaemia
- hyperkalaemia causes depolarisation of excitable cells
- alkalosis: the opposite effect
What are the sources of acids and bases in humans?
Hint - P, S, bases and FAs, lactic acids
- directly from food or metabolism
1. food - proteins contain phosphorus and sulphur
- converted to phosphoric and sulphuric acid (strong acids)
- fruit digestion yields release of bases
2. metabolism - fatty acids
• from fat metabolism
• weak acids, yield protons - lactic acid
• anaerobic glycolysis (muscles, hard exercise)
• weak acid, yields protons
Describe the role of carbonic acid in metabolism.
- CO₂ from respiring cells hydrated to form carbonic acid (weak acid):
CO₂ + H₂O → H₂CO₃ → HCO₃- + H⁺ - first step catalysed by carbonic anhydrase
- reaction freely reversible at lungs, etc
- respiring cells produce vast quantities of carbonic acid
- note H₂CO₃ is very difficult to measure, however, relationship with CO₂ in solution depends on Pco₂ and its solubility (α)
Which three mechanisms are available for neutralisation of acids/bases and within which time scales?
(Hint - the most obvious, lung making up, kidneys making up)
- blood buffers (seconds)
- respiratory compensation (minutes)
- renal compensation (hours to days)
Essentially, what is a blood buffer?
Hint - a modified acid/base
a weak acid/base which can “absorb” protons/conjugate bases (HA → H⁺ + A-)
Substituting known physiological values: pK = 6.1, [HCO3-] (mM) = 25, Pco₂ (mmHg) = 40, Α = 0.03. What do you calculate the pH to be?
(Hint - one of these values is just a distractor)
- pH = 6.1 + log10([25]/40)
= 5.895 (3 d.p.)
In which two ways can blood pH be altered to regulate pH and via which organs?
- Altering:
• CO₂ concentration (lungs)
• HCO₃- concentration (kidneys)
What is a Davenport plot (see notes) used for?
Hint - olden-day acid stuff
to manually calculate and diagnose acid-base imbalances using H-H equation parameters
What is:
a) respiratory acidosis? (Hint - more CO₂)
b) respiratory alkalosis? (Hint - less CO₂)
c) metabolic acidosis? (Hint - more acid)
d) metabolic alkalosis? (Hint - more base)
a) increased CO₂ causes increased bicarbonate and decreased H⁺ which causes pH to decrease (acidic)
b) decreased CO₂ causes decreased bicarbonate and increased H⁺ which causes pH to increase (alkaline)
c) if you add acid, pH and bicarbonate decrease
d) if you add base, pH and bicarbonate increase
What are three other buffer systems in the body other than carbonic acid?
(Hint - blood molecule, pps and P)
- Haemoglobin
- Plasma proteins
- Phosphate
Describe the Haemoglobin buffering system.
Hint - Hb = the carbonic acid system but with a mop and involvement of the lungs
- buffers metabolically produced CO₂
CO₂ + H₂O ⇌ H₂CO₃ ⇌ HCO₃- + H⁺ - H⁺ is mopped up by reduced haemoglobin (Hb)
H⁺ + Hb ⇌ HHb - haemoglobin reduced after O₂ delivery to cells
- in lungs O₂ is high and the situation reversed
- this liberates CO₂, removing excess acid
Describe the plasma protein buffering system in ECF.
(Hint - the building blocks of proteins with which charge of R-groups, most important buffer where, carboxyl groups, amino groups)
- AAs in proteins have acidic and basic R-groups and so are amphoteric (+VE and -VE)
- most important buffer is in ICF where [protein] high
- carboxyl R-groups = weak acids (COOH ⇌ COO- + H⁺)
- amino R groups = weak bases (NH₂ + H⁺ ⇌ NH₃⁺)
Describe the role of the phosphate buffering system in ECF.
(Hint - size of role and why, second to which other system aminos, when is it a good urinary buffer, equation to do with the phosphate-related acid)
- minor role due to low concentration
- second to proteins in ICF acid-base balance
- good urinary buffer under normal conditions (little reabsorption)
- H₂PO4 ⇌ HPO4- + H⁺
What is respiratory compensation and what does it predict?
Hint - HH equation, to do with the effect of a pH decrease on Pco₂ , CO₂ solubility, hence levels of CO₂ removal
- the Henderson-Hasselbalch equation:
pH = pK + log10([HCO₃-]/Pco₂): - predicts that if pH decreases then likely that Pco₂ will be increased
- CO₂ solubility (α) is low (0.03)
- so, most CO₂ is gaseous, so can be removed by lungs
How is increased Pco₂ detected?
Hint - c in one location, p in another → change in what measurement for each one
- central chemoreceptors (brainstem) → change in CO₂
- peripheral chemoreceptors (aortic arch, cb) → change in H⁺
What is the response to increased Pco₂ which drops pH?
Hint - effect on CO₂ levels, detected by which areas/receptors, causes increased v, effect on blood pH
- CO₂ is increased (see notes)
- detected by brainstem/peripheral chemoreceptors
- causes increased ventilation to blow off CO₂
- this increases blood pH (-VE feedback)
If a change in acid-base balance is due to changes in CO₂ arising from respiratory disease, what does this mean for the respiratory compensatory mechanism?
(Hint - less of a role so more for others)
- it cannot contribute to restoration of pH balance
- other buffers and renal compensatory mechanisms become important
What is renal compensation?
Hint - kidney takes 3 different actions all of which involves the 2 main ions HCO₃- in and H⁺ out
- H-H equation predicts a pH decrease → bicarbonate decrease
- kidney compensates by making HCO₃- reabsorption and H⁺ secretion:
• slower (hours/days)
• more efficient at restoring pH balance
• every 1 HCO₃- absorbed → 1 H⁺ secreted into urine - pH regulated by change in CO₂ in respiratory compensation
What is the renal compensation mechanism in acidosis?
Hint - plasma H⁺ → HCO₃- → renal H⁺ → change in urine pH
- plasma [H⁺] increases
- less HCO₃- filtered as it buffers increased H⁺
- renal H⁺ secretion increases
- urine becomes more acidic
What is the renal compensation mechanism in alkalosis?
Hint - plasma H⁺ → HCO₃- → effect on renal HCO₃- as H⁺ is also affected → change in urine pH
- plasma [H⁺] decreases
- more HCO₃- filtered as less required for buffering
- not all HCO₃- reabsorbed as H⁺ availability is rate-limiting
- urine becomes more alkaline
How can urine be buffered during acidosis?
Hint - to acidify urine during acidosis, a particular gradient needed, used by buffers mopping up an ion in urine
to acidify urine, the gradient for H⁺ secretion must be maintained → done by H⁺ being mopped up by buffers in urine
How is the H⁺ secreted in urine buffered?
Hint - by two types of buffer → PO4 and NH
- Phosphate (H₂PO4 ⇌ HPO4- + H⁺)
- capacity limited
- in acidosis, capacity exceeded - Ammonia (NH₃ + H⁺ ⇌ NH4⁺)
- secreted in kidney
- weak base
- produced from glutamine metabolism
- production up-regulated during acidosis
- ammonia in collecting ducts mops up urinary H⁺ during acidosis
What are compensation and correction?
Hint - compensation is just the main change, correction is changing all 3 things → pPH
- compensation: corrects pH change ONLY (with Pco₂ and HCO₃- usually sacrificed) and comes into play immediately
- correction: complete restoration of pH, Pco₂ and HCO₃-
What does a respiratory acid-base imbalance generally cause?
Hint - change in p to do with CO₂ → changing H⁺
change in pH associated with abnormal Pco₂ → causes changes in carbonic acid-derived H⁺
What does a metabolic acid-base imbalance generally cause?
change in pH associated with altered [HCO₃- ] due to participation of HCO₃- in abnormal buffering
What is respiratory acidosis:
a) caused by? (Hint - more of an acidic gas)
b) its uncompensated result? (Hint - pH and HCO₃-)
c) method of pH restoration? (Hint - HCO₃- and ammonium)
d) its positions on the Davenport plot? (Hint - think of the numbers/values for acidosis)
a) retention of CO₂ (hypoventilation)
b) pH decreases, HCO₃- increases (B)
c) methods:
- increased reabsorption of HCO₃- → remains elevated
- secretion of ammonium
d) normal position is A and new position C
What is the time course of respiratory/meabolic acidosis/alkalosis with:
a) acute intracellular buffering?
b) chronic renal compensation?
(Hint - chronic means long-term)
a) seconds, minutes
b) days
What are the clinical causes of respiratory acidosis?
Hint - not mind but lungs, heart and respiratory centres → DEP
- drug-induced depression of respiratory centres
- pulmonary oedema (fluid on lungs)
- emphysema
What is respiratory alkalosis:
a) caused by? (Hint - less acid gas- hyperv)
b) what is the uncompensated result? (Hint - pH down and vice for HCO₃-)
c) pH restoration methods? (Hint - less HCO₃- and A)
d) its positions on the Davenport plot?
a) loss of CO₂ (hyperventilation)
b) pH increases, HCO₃- decreases
c) compensated result:
- decreased reabsorption of HCO₃- → remains depressed
- decreased secretion of ammonium
d) A (normal position) → B → C-D
What are the clinical causes of respiratory alkalosis?
Hint - all mind-based, physical harm, too much paracetamol A, aeroplanes → hapa
- anxiety, fear
- pain
- aspirin poisoning
- high altitude
What is metabolic acidosis:
a) caused by,
b) its uncompensated result
c) methods of pH restoration?
d) its positions on the Davenport plot?
a) loss of HCO₃- or addition of H⁺ to plasma
b) pH decreases, HCO₃- decreases (B)
c) restored by:
- respiratory compensation (increased ventilation) partially restores pH
- renal compensation completes restoration of pH by increasing HCO₃ reabsorption
d) normal A and abnormal → C
What are the clinical causes of metabolic acidosis?
Hint - too many fats diet for glycaemics, too muhc fluid in faeces, going too hard at gym, kidneys - dhdr
- diabetic keto-acidosis (abnormal fat metabolism)
- diarrhoea (loss of HCO₃-)
- heavy exercise (addition of lactic acid)
- renal failure (reduced secretion of protons)
What is metabolic alkalosis:
a) caused by?
b) its uncompensated result?
c) methods of pH restoration?
d) its positions on the Davenport plot?
a) addition of HCO₃- or loss of H⁺ from plasma
b) pH increases, HCO₃- increases
c) compensated by:
- respiratory compensation (increased ventilation) partially restores pH
- renal compensation completes the restoration of pH by decreasing reabsorption of HCO₃-
d) (normal) A → B → C (abnormal)
What are the two main clinical causes of metabolic alkalosis?
(Hint - too much chest burn meds and throwing up)
- ingestion of antacids
- vomiting (loss of HCl)
Why is respiratory compensation for metabolic alkalosis complex and variable? (Hint - O₂ shortage limits response)
response limited by hypoxaemia (due to hypoventilation) which counteracts response via chemoreceptors
If limiting factors absent, what would happen at the start of respiratory compensation?
the initial reduction in ventilation would be seen to varying degrees
In metabolic alkalosis, which response is the most effective at causing compensation (pH restoration)?
(Hint - the H+ organ)
the renal response
