25. Acid-Base Balance Flashcards
Why is pH important in human physiology?
Define acid and base.
What is the body’s pH range (venous to arterial)?
Which pH ranges, once crossed, mean death?
Enzymes that facilitate the chemical reactions of the body have pH optima. Also intracellular pH varies greatly - tightly regulated in cell. pH controls speed of biochemical reactions. Synaptic function also depends on intra and extracellular pH gradients.
Acid: H+ donator; base: H+ acceptor
Venous: 7.35 (below = acidosis/acidaemia), Arterial: 7.45 (above = alkalosis/alkalaemia)
<6.8 - >8.0
Where is the main origin of H+ ions?
What effect does a disease state have on acid formation?
What 3 mechanisms does the body have to limit pH changes/regulate concentration of H+?
Human diet = almost neutral. Most from cellular metabolism -> prod lots carbonic, sulphuric, phosphoric and other acids constantly! E.g acids prod druing food breakdown e.g. sulphuric, CO2 metabolically pord and form carbonic acid with H2O, lactic acid from exercise.
In disease states even more acid may be prod e.g. keto acids in diabetes, CO poisoning, drugs and hypoxia all lead to lactic acid, methanol poisoning -> formic acid.
1) Chemical buffer systems in blood and ICF - immediate
2) Respiratory centre in BS - 1-3 minutes
3) Renal mechanisms - hours - days
Explain the “immediate-action” method of regulating H+ concentration in the body?
Chemical buffer systems in blood and ICF: 3 major buffer systems = bicarbonate (HCO3-), proteins (Hb and albumin), phosphate (PO43-)(most imp within cells). Resist small pH changes. Weak acid and salt of that acid.
What are the average values (in mmol/L) for the following cations and anions that make up the anion gap: K+, Na+, HCO3-, Cl-?
What is the anion gap? Give the calculation and value.
What are the unmeasured cations and anions?
K<strong>+</strong> = 4, Na+ = 140, HCO3- = 24, Cl- = 104
Difference between measured cations and measured anions in serum. Calculated by: [Na+] - ([Cl-] + [HCO3-]) = 8 to 12 mEq/L (K+ usually so small it’s ignored. If added in: ([Na+] + [K+]) - ([Cl-] + [HCO3-]) = 12 to 16 mEq/L)
Cations: Ca2+, Mg2+, proteins
Anions: phosphates, sulphates, proteins
How can you get a normal anion gap but metabolic acidosis? What is this called?
List some causes.
How can a deficiency in the kidney cause this?
HCO3- reduced (e.g. lost through gut) but it’s compensated by Cl- (HCO3- pumper out of cell in exchange for Cl- pumped into cell, but Cl- does not belong in cell so it pumped back out into plasma(see pic)). Thus bicarb loss compensated for by chloride increase = hyperchloremic metabolic acidosis.
Severe diarrhoea, chronic laxative abuse, villous adenoma, external drainage of pancreatic/biliary secretions (e.g. fistulas, loses via NG tubes, adminsitration of acidifying salts, urinary diversions
If unable to excrete acids (H+) efficiently then more HCO3- needed to buffer them = drop in HCO3-. Cl- pumped back out of cell so get same situation. Caused by renal failure and renal tubular acidosis type 1 and 4
Describe elevated gap acidosis.
List some causes
Increase in unmeasured anions so losing HCO3-. Not compensated for by Cl- so see increase in cations.
Ketoacidosis, lactic acidosis (and others e.g. formic acid accumulation), renal failure, toxic ingestions. SEVERE renal failure
Describe low gap acidosis, and what it’s called.
List some causes.
When albumin is lost - it’s the major unmeasured anion and contributes almost to whole value of anion gap. Hypoalbuminemea.
Hemorrhage (keep losing albumin in blood), nephrotic syndrome (kidneys prevent albumin entering urine), intestinal obstruction (rare, malabsorption), liver cirrhosis (b/c it’s produced in liver)
After chemical buffer systems in the blood and ICF, what is the 2nd line of defence of blood pH?
Why are kidneys considered the ‘ultimate acid-base regulatory organs)? (3rd line of defence).
What 2 things must the kidney do to maintain acid base balance, and how does it do these things?
Respiratory system. (CO2 constantly prod from metabolism. Lungs ONLY deal with volatile acids)
Renal control of pH. Only kidneys can rid body of metabolic acids such as phosphoric acid, uric acid, lactic acid, ketones and prevent metabolic acidosis.
1) reabsorb all filtered HCO3- 2) excrete daily acid load
Manages via H+ secretion, HCO3- reabsorption and excretion of H+ ions with urinary buffers = titratable acids (e.g. H+ + HPO42- -> H2PO4-) and ammonium.
What percentage of filtered bicarb (main buffer in plasma) does the PCT reclaim?
What is carbonic anhydrase, and how does it work at the PCT?
Does reclaiming HCO3- with active H+ exretion only occur in the PCT?
70-90% (and the rest further down the kidney tubule)
At brush border, facilitates H2O + CO2 <-> H2CO3 <-> H+ + HCO3-. It converts bicarb to CO2 and OH- in tubule lumen. CO2 diffuses into cell. OH- combines with H<strong>+</strong> = H2O and enters cell via aquaporin/diffusion. Antiporter puts Na+ into cell from tubular lumen. CA facilitates reconversion of HCO3- in cell. HCO3- and Na+ symporter (b/c don’t want Na+ in cell) transports them both to interstitial space. H+ always being pumped out to tubule lumen.
No - almost everywhere in kidney, pump preserves neutrality in cell
What are intercalated cells and how do they work?
Describe the kidney’s hormonal (and non) regulation of acid-base status.
What happens if pH drops in CD and CDT?
How does a pH drop influence PTH?
A type of kidney collecting duct cell, α and β varieties, ‘reversed polarity’. Sometimes body in acidosis/alkalosis so need to be able to adjust it. α-intercalated cells secrete H+ and reabsorb HCO3- (e.g. if in acidosis); β-intercalated cells secrete HCO3- and reabsorb H+ (e.g. if in alkylosis)
Diff pH sensors in kidney, sense pH drop = respond via angiotensin II, aldosterone and parathyroid hormone.
Aldosterone = reabsorb Na+ and ret rid of K+ and H+. If hypokalemia, K+ reabsorbed via antiporter which gets rid of more H+.
Prevents reabsorption of phosphate buffer, and if not, its used to trap H+ and excrete it
What do the following lead to, and why:
a) acidemia?
b) alkalemia?
What happens in the renal tubule cell when the body is in acidosis?
a) Acidemia leads to hyperkalemia: H+ in cells and conjugated to protein = displaces K+ -> released into blood
b) Alkalemia leads to hypokalemia: causes cells to take up K+
Bicarb broken down in blood by H+ to H2O and CO2, taken into cell, reformed in cell and split to H+ and HCO3- (diffuses back to blood). Get rid of H+ to lumen via Na+/H+ transporter. Don’t want Na+ in cell so trade it for K+ from blood to keep electrical neutrality. Override acidosis in lumen via phosphate buffer (H+ + HPO42- -> H2PO4-)or excrete NH3 from cell -> combines with H+ to make NH4+
What happens in the renal tubule cell when the body is in alkylosis?
What is compensation?
What are the steps to diagnosing acid-base imbalance?
Tubular cells secrete HCO3- ions using antiporter with Cl-, and reclaim H+ to acidify blood, using seperate ATPases which can actively secrete H+. The K+ are traded for H+.
Have 2 organs deaing with the carbonic acid on both sides of the equation: CO2 + H2O = LUNGS, H+ + HCO3- = KIDNEY. So if a problem with one side, can compensate with other side (but will never be as good).
Is pH low (acidosis) or high (alkalosis)? What is PaCO2 value? (respiratory indicator). What is HCO3- value? (metabolic indicator). Base for interpretation of ABG!
Describe the 4 forms of acid-base disturbance, including causes.
1) Respiratory acidosis: CO2 retention - hypoventilation (COPD etc.). Renal compensation (H+ excretion, HCO3- gain)
2) Respiratory alkylosis: CO2 loss - hyperventilation (anxiety, altitude). Renal compensation (H+ gain, HCO3- excretion)
3) Metabolic acidosis: Gain of acid, loss of base (diarrhoea, keto-acidosis, lactic acidosis). Respiratory compensation (CO2 loss, HCO3- falls)
4) Metabolic alkylosis: Loss of acid, gain of base (vomiting, hypokalemia, ingestion of HCO3-). Respiratory compensation (CO2 and HCO3- rise)
