Fill in the blanks
Why is maintained H+ within tight limits important?
- Protein folding is effected by pH
- Molecules are ionised- their state of ionisation depends on PH
Name the 3 major components of acid-base regulation
- Ability to buffer
- Ability to ventilate
- Abilty of the kidneys to regulate the pH through secretion and rebasorption
Which acid-base regulation component is able to defend against acidosis immediately?
Buffering system
Which acid-base regulation component is able to defend against acidosis rapidly but not immediately?
Increase in ventilation
Which acid-base regulation component is able to defend against acidosis slowly?
Renal adjustment
How does the buffering system regulate acid-base homeostasis during acidotic states
CO2 + H20 <-> H+ + HCO3
Gain of H+ (during acidosis) leads to the equation being driven to the carbon dioxide end.
More CO2 and H20 formed to reduce the H+ levels
How does the buffering system regulates acid-base homeostasis during alkoltic states
CO2 + H20 <-> H+ + HCO3
Loss of H+ leads to the equation being driven to the hydrogen end.
More H+ and HCO3 and less CO2 and H20 formed
Name the buffers found in the body
Plasma proteins
Phosphate
Bicarbonate
Haemoglobin
Bone
PO4
In which fluid compartment of the body does buffering occur?
Extracellular fluid and intracellular fluid
Carbon dioxide is a?
A) Volatile acid
B) Fixed acid
A) Volatile acid
Meaning it can be eliminated from the body as a gas
Give an example of a volatile acid
CO2
Give an example of a fixed acid
Dietary acids and acid produced by anaerobic respiration are “fixed” – they cannot be “converted “ to CO2
How are fixed and volatile acids excreted by the body?
Volatile acid: excreted from the body as gas
Fixed acids: buffered with HCO3
The kidneys secrete ___ acids
Fixed
What are the two main systems the kidneys use to secrete fixed acids
- Ammonia (NH4) system
- Bicarbonate (PO4)mechanism
What are the 3 ways in which the kidneys regulate acid-base balance
- Reabsorb filtered HCO3
- Secrete fixed acid
- Ammonia system
- Bicarbonate system
Reabsorption of HCO3 occurs where in the kidneys?
Largely in the proximal convoluting tubule
Small contributions from the distal convoluting tubule and the thick ascending loop of Henle
What happens if there is an inability to reabsorb filtered HCO3
Metabolic acidosis
Define GFR
Glomerular filtration rate
It is the amount of blood that is being presented to the glomerulus per minute
How much HCO3 is reabsorbed by the kidneys?
(virtually) all filtered HCO3 is reabsorbed
Describe the generic mechanism for reabsorbing bicarbonate
Filtered bicarbonate binds to secreted hydrogen ions and by the action of carbonic anhydrase causes the formation of water and carbon dioxide
The water and carbon dioxide enter the tubular cell and through the action of carbonic anhydrase forms hydrogen ion and bicarbonate.
The bicarbonate is transported into the interstitium back into the body.
Hydrogen ion is secreted back into the tubule lumen
Which system is accounts for more acid excretion
A) Excretion of ammonium
B) Titration of phosphate
A) Excretion of ammonium -accounts for 50- 100 mmol H+/day
B) Titration of phosphate - only accounts for 40 mmol H+/day
•Each H+ excreted is matched by what?
The generation of a new HCO3 which is absorbed
What is the limits of the respiratory compensation
There is a limit to how hard patients can drive ventilation without tiring, and they can’t stop breathing
Diagnosing acid-base disorders requires what?
Knowledge of H+, HCO3, CO2 (blood gases), electrolytes (Na, K, Cl) and a clinical history
What are the mechansim of compensation with acid-base disorders
- Renal compensation
- Respiratory compensation- may not be complete
What are the 3 most common cause of metabolic acidosis
-
Addition of extra acid
- Generation of organic acid through metabolism – lactic acidosis, keto-acidosis
- Ingestion of acid (e.g. methanol)
-
Failure to excrete acid
- Renal tubular acidosis
-
Loss of HCO3
- In stool (diarrhoea) or urine (“renal tubular acidosis”)
What is the primary abnormality in metabolic acidosis
Fall in plasma HCO3
Loss of bicarbonate is like adding a hydrogen into the system.
What are the systemic effects of metabolic acidosis
- Cardiovascular system
- Arrythmias, ↓cardiac contractility, vasodilation
- Respiration
- ↑ventilation (Kussmaul’s breathing)
- Metabolic
- Protein wasting, resorption of Ca from bone
- Other
- Neutrophilia
Define anion gap
Represents the concentration of all the unmeasured anions in the plasma.
Which anion makes up the majority of the unmeasured anion represented by the anion gap under normal circumstances.
The negatively charged proteins account for about 10% of plasma anions
What is the equation for the anion gap
Anion gap = [Na+] - [Cl-] - [HCO3-]
What must be adjusted for in the anion gap
Must adjust for low albumin
Describe lactic acidosis
- Lactic acid produced through glycolytic metabolism of pyruvate
- Lactic acid is buffered by HCO3 to lactate and then metabolised in liver (and kidney to some extent)
- Production of lactic acid is vastly greater than renal excretion of H+
- Acidosis usually results from hypoperfusion and reduced hepatic clearance – major problem in sepsis
What can cause lactic acidosis
Medications (metformin)
Liver failure
Poisoning (cynaide, aspirin)
What is the primary abnormality in metabolic alkalosis
Primary abnormality is ¯ H+ and HCO3
High PCO2 is refers to as:
A) Hypoventilation
B) Hyperventilation
A) Hypoventilation
Reduced ventilation results in the high CO2 as less CO2 is getting blown off
Low PCO2 is refers to as:
A) Hypoventilation
B) Hyperventilation
B) Hyperventilation
High ventilation results in the low CO2 as more CO2 is getting blown off
What are the main causes of metabolic alkalosis
Vomiting- loss of gastric acid
Diuretics
aka volume depletion
Bicarbonate reabsorption in distal convoluting tubule requires the section of which electrolyte
Chloride
What is the treatment for acidosis and alkalosis
Main way to treat acidosis/alkaliosis- treat the cause removing the underlying tendency for acid/alkaline- the body will sort it out itself as it has a mechanisms to do so