Acid Base Balance And Osmolarity Flashcards
What is the reference range for plasma H+ ions?
35.5 - 44.5 nmol/L
How does alkalosis affect calcium?
Lowers free Ca2+
Causes Ca2+ ions to come out of solution
Increased neuronal excitability
Paraesthesia and tetany
How does acidosis affect proteins?
Decreased pH due to increased H+ ions
Disturbs/denatures enzymes
Affects muscle contractility, glycolysis and hepatic function
About which pH do we consider acidosis severe and then life threatening?
Severe < 7.1
Life threatening < 7.0
What number is the constant pK in the Henderson-Hesselbach equation?
6.1
What is the normal physiological pH?
7.4
How would respiratory acidosis occur?
Hypoventilation
Leads to hypercapnia (increased CO2 in plasma)
This decreases plasma pH
Causing acidosis
How does respiratory alkalosis occur?
Hyperventilation causes hypocapnia in the plasma
Fall in CO2 causes increase in pH
Alkalosis
How is respiratory acidosis compensated for?
Kidneys increase the level of bicarbonate
How is respiratory alkalosis compensated for?
Kidneys decrease the concentration of bicarbonate
What is metabolic acidosis?
A fall in pH due to a fall in conc of bicarbonate
Can be compensated for by increased ventilation
What is metabolic alkalosis?
A rise in plasma bicarbonate which can only be partially compensated by decreasing ventilation
What is a common cause of metabolic alkalosis?
Repeated vomiting
How do the kidneys increase bicarbonate levels?
Excrete less bicarbonate in the urine
Make more bicarbonate
What do the kidneys use to make bicarbonate?
Kidneys have a high conc of CO2 due to their high metabolic rate - react this with water to form bicarbonate
Also can make bicarbonate from amino acids
(This means ammonium will be present in the urine)
Where does the majority of bicarbonate reabsorption take place?
PCT
80%
Describe the mechanism for reabsorption of bicarbonate
Na/K/ATPase on basolateral membrane creates the Na+ gradient
Na+ enters cell in exchange for H+ (NHE on apical membrane)
H+ reacts with the bicarbonate to form CO2 and water which can diffuse into the cell
In the cell it is reconverted into HCO3- and H+
HCO3- passes out of the cell via the Na-HCO3 symporter on the basolateral membrane
Which amino acid is used to produce bicarbonate?
Glutamine
What is the minimum urine pH?
4.5
Should there be HCO3- in the urine normally?
No
How is acid in the urine excreted?
Buffered by phosphate (titratable)
Reacted with NH3 = NH4+
What is the normal H+ excretion per day?
50 - 100 mmol/day
Why do we excrete acid in the urine?
To maintain the concentration of bicarbonate in the plasma
How does a decreased pH affect the kidneys in order to correct itself??
Enhances activity of Na+/H+ exchanger
Enhances ammonium production in PCT
Enhances activity of H+/ATPase in DCT
Increased capacity to export HCO3- into ECF
What is the anion gap?
Difference between the cations (Na+/K+) and the anions (HCO3-/Cl-)
(Normal = 10 - 15 mmol/L as there are unaccounted anions)
Why does the anion gap increase?
Anions from (paired to) metabolic acids replace HCO3- (Other than Cl-)
Do all forms of metabolic acidosis create an anion gap?
No
How do we treat metabolic alkalosis?
Give them an infusion of bicarbonate
(Sounds backwards)
Causes a rapid excretion of bicarbonate so their levels will reduce
Why is there a problem if there is an alkalosis and a volume depletion?
Capacity to lose bicarbonate is reduced because of high rate of Na+ recovery
HCO3- will be reabsorbed with the Na+
How does hypokalaemia affect the kidneys?
K+ moves out of tubule cells in exchange for H+
This makes the cells more acidic
Favours H+ excretion and HCO3- reabsorption
Leading to alkalosis
How does hyperkalaemia affect the kidneys?
K+ moves into tubule cells in exchange for H+
Makes the cells more alkaline
Favours H+ reabsorption and HCO3- excretion
Can lead to acidosis
What is a normal cell osmolarity?
~ 300 mOsm/kg
What is the osmolarity of urine in a normally hydrated person?
500 - 700 mOsm/kg
Where are the osmoreceptors located and why is this a good location?
In the OVLT of the hypothalamus
(Organum vasculosum of the lamina terminalis)
Has fenestrated endothelium therefore in direct correct with the plasma to sense osmolarity
What are the 2 responses to an increase in osmolarity?
Thirst - behavioural
ADH - increased renal water reabsorption
Why are cells of the supraoptic nucleus close to the OVLT?
Baroreceptors are found here
Therefore changes in BP can cause the release of ADH
When facing a massive fluid loss, what is the body’s priority?
Saving volume to prevent circulatory collapse
Sacrifice the osmolarity in order to stay alive
Describe the delay in correction regarding thirst
Drinking water takes time to correct the osmolarity
However our thirst sensation goes away before it is corrected to prevent us over-drinking
What is a regulatory appetite?
Having cravings for something that we have a deficiency in
The body needs it
Where is ADH produced and secreted?
Produced = hypothalamus Secreted = posterior pituitary gland
How does ADH work?
Increases the number of AQP2 channels in the apical membrane of cells in the collecting duct of the nephron
Increases water uptake
Describe central diabetes insipidus
ADH levels are too low for the osmolarity
Due to damage in hypothalamus/pituitary gland
Large quantity of urine produced
Decreased blood volume
Describe nephrogenic diabetes insipidus
Insensitivity of the kidney to ADH
(Even though ADH levels are appropriate)
Produce large volumes of dilute urine
How do we treat diabetes insipidus?
ADH injections or a nasal spray
What is SIADH?
Syndrome of inappropriate antidiuretic hormone secretion
Excessive release of ADH
Dilutional hyponatraemia occurs
(Increased water reabsorption, conc of Na+ decreases)
Briefly describe the counter current mechanism of the LOH
Juxtamedullary nephrons have a long loop of Henle to establish a vertical osmotic gradient
Vasa recta help to preserve that gradient due to a blood flow in the opposite direction
What is the most crucial part of the LOH for generating the gradient?
Thick ascending limb
Pumps Na+ into medulla via NKCC2
Is impermeable to water so water cannot follow
Describe what happens to urea in the nephron
Some reabsorbed in PCT
Some moves into the interstitium via AQPs with water to increase osmolarity of medulla (increase water reabsorption)
Diffuses back into filtrate when conc urea higher in interstitium
Some excreted in urine
How does the vasa recta help to maintain the medullary concentration gradient?
Taking up all the water that leaves of the loop of henle
(Otherwise the water would decrease the conc in the medulla)
Flow is in the opposite direction therefore high osmotic blood is near to low osmotic filtrate so that the water moves more easily into the vasa recta
