Regulation of Intracellular Hydrogen Ion Concentration

Importance of Intracellular [H⁺]

The most important [H⁺] for the body is the intracellular [H⁺]

Why? Because of its profound effects on metabolism and other cell processes which occur due to the effects of [H⁺] on the degree of ionisation of intracellular compounds. Specifically:

• Small molecule effect: Intracellular trapping function -due to the ionisation of metabolic intermediates.
• Large molecule effect: Effects on protein function: The function of many intracellular proteins (esp the activities of enzymes) is altered by effects on the ionisation of amino acid residues (esp histidine residues)

Renal Regulation of Acid-Base Balance

The organs involved in regulation of external acid-base balance are the lungs are the kidneys.

The lungs are important for excretion of carbon dioxide (the respiratory acid) and there is a huge amount of this to be excreted: at least 12,000 to 13,000 mmols/day.

In contrast the kidneys are responsible for excretion of the fixed acids and this is also a critical role even though the amounts involved (70-100 mmols/day) are much smaller. The main reason for this renal importance is because there is no other way to excrete these acids and it should be appreciated that the amounts involved are still very large when compared to the plasma [H⁺] of only 40 nanomoles/litre.

There is a second extremely important role that the kidneys play in acid-base balance, namely the reabsorption of the filtered bicarbonate. Bicarbonate is the predominant extracellular buffer against the fixed acids and it important that its plasma concentration should be defended against renal loss.

In acid-base balance, the kidney is responsible for 2 major activities:

• Reabsorption of filtered bicarbonate: 4,000 to 5,000 mmol/day
• Excretion of the fixed acids (acid anion and associated H⁺): about 1 mmol/kg/day.

Both these processes involve secretion of H⁺ into the lumen by the renal tubule cells but only the second leads to excretion of H⁺ from the body.

The renal mechanisms involved in acid-base balance can be difficult to understand so as a simplification we will consider the processes occurring in the kidney as involving 2 aspects:

• Proximal tubular mechanism
• Distal tubular mechanism

Respiratory Regulation of Acid-Base Balance: Acid Base Learner Series

How is the Respiratory System Linked to Acid-base Changes?

‘Respiratory regulation’ refers to changes in pH due to pCO2 changes from alterations in ventilation. This change in ventilation can occur rapidly with significant effects on pH. Carbon dioxide is lipid soluble and crosses cell membranes rapidly, so changes in pCO2 result in rapid changes in [H+] in all body fluid compartments.

A quantitative appreciation of respiratory regulation requires knowledge of two relationships which provide the connection between alveolar ventilation and pH via pCO₂. These 2 relationships are:

• First equation - relates alveolar ventilation (V_A) and pCO₂
• Second equation - relates pCO₂ and pH.

Acid Base Learner Series: Buffers

Definition of a Buffer

A buffer is a solution containing substances which have the ability to minimise changes in pH when an acid or base is added to it ¹.

A buffer typically consists of a solution which contains a weak acid HA mixed with the salt of that acid & a strong base eg NaA. The principle is that the salt provides a reservoir of A^- to replenish [A^-] when A^- is removed by reaction with H⁺.

Buffers in the Body

The body has a very large buffer capacity.

This can be illustrated by considering an old experiment (see below) where dilute hydrochloric acid was infused into a dog.

Acid Base Physiology: Acid Base Learner Series

Acid Base Physiology

Each day there is always a production of acid by the body’s metabolic processes and to maintain balance, these acids need to be excreted or metabolised. The various acids produced by the body are classified as respiratory (or volatile) acids and as metabolic (or fixed) acids. The body normally can respond very effectively to perturbations in acid or base production.

Respiratory Acid

The acid is more correctly carbonic acid (H₂CO₃) but the term 'respiratory acid' is usually used to mean carbon dioxide. But CO₂ itself is not an acid in the Bronsted-Lowry system as it does not contain a hydrogen so cannot be a proton donor. However CO₂ can instead be thought of as representing a potential to create an equivalent amount of carbonic acid. Carbon dioxide is the end-product of complete oxidation of carbohydrates and fatty acids. It is called a volatile acid meaning in this context it can be excreted via the lungs. Of necessity, considering the amounts involved there must be an efficient system to rapidly excrete CO₂.

The amount of CO₂ produced each day is huge compared to the amount of production of fixed acids. Basal CO₂production is typically quoted at 12,000 to 13,000 mmols/day.

Basal Carbon Dioxide Production Consider a resting adult with an oxygen consumption of 250 mls/min and a CO2 production of 200 mls/min (Respiratory quotient 0.8): Daily CO2 production = 0.2 x 60 x 24 litres/day divided by 22.4 litres/mole = 12,857 mmoles/day.

Increased levels of activity will increase oxygen consumption

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Acid Base Learner Series: Respiratory Acidosis in detail

A respiratory acidosis is a primary acid-base disorder in which arterial pCO₂ rises to a level higher than expected.

At onset, the acidosis is designated as an 'acute respiratory acidosis'. The body's initial compensatory response is limited during this phase.
As the body's renal compensatory response increases over the next few days, the pH returns towards the normal value and the condition is now a 'chronic respiratory acidosis'.
The differentiation between acute and chronic
is determined by time but occurs because of the renal compensatory response (which is slow).

 Causes of Respiratory Acidosis:
The arterial pCO₂ is normally maintained at a level of about 40 mmHg by a balance between production of CO₂ by the body and its removal by alveolar ventilation. If the inspired gas contains no CO₂ then this relationship can be expressed by:

paCO₂ is proportional to V_CO2 / V_A

where:
V_CO2 is CO₂ production by the body
V_A is Alveolar ventilation

An increase in arterial pCO₂ can occur by one of three possible mechanisms:

• Presence of excess CO₂ in the inspired gas
• Decreased alveolar ventilation
• Increased production of CO₂ by the body

CO₂ gas can be added to the inspired gas or it may be present because of rebreathing : Anaesthetists are familiar with both these mechanisms. In these situations, hypercapnia can be induced even in the presence of normal alveolar ventilation and normal carbon dioxide production by the body.
An adult at rest produces about 200mls of CO₂ per minute

Acid Base Balance Series: What is the 'osmolar gap'?

NB: 'Osmolar gap' has several alternative names: 'osmol gap', 'osmole gap', 'osmolarity gap' & 'osmolal gap'; these all refer to the same thing. For consistency, the term "osmolar gap" is used exclusively through this book.

What is the 'osmolar gap'?

Definitions An osmole is the amount of a substance that yields, in ideal solution, that number of particles (Avogadro’s number) that would depress the freezing point of the solvent by 1.86K Osmolality of a solution is the number of osmoles of solute per kilogram of solvent. Osmolarity of a solution is the number of osmoles of solute per litre of solution.

So osmolality is a measure of the number of particles present in a unit weight of solvent. It is independent of the size, shape or weight of the particles. It can only be measured by use of a property of the solution that is dependent on the particle concentration. These properties are collectively referred to as Colligative Properties. Osmolality is measured in the laboratory by machines called osmometers. The units of osmolality are mOsm/kg of solute
Osmolarity is calculated from a formula which represents the solutes which under ordinary circumstances contribute nearly all of the osmolality of the sample. There are many such formulae which have been used. One widely used formula for plasma which is used at my hospital is:

Calculated osmolarity = (1.86 x [Na⁺]) + [glucose] + [urea] + 9

Note regarding units: For the above equation, all concentrations are in mmol/l, and not mg/100mls. The result will then be in mOsm/l of solution. This equation is often expressed differently in North America where glucose & blood urea nitrogen (BUN) are reported in

Acid Base Learner Series: The Urinary Anion Gap

The Urinary Anion Gap

The cations normally present in urine are Na⁺, K⁺, NH₄⁺, Ca⁺⁺ and Mg⁺⁺.
The anions normally present are Cl^-, HCO₃^-, sulphate, phosphate and some organic anions.
Only Na⁺, K⁺ and Cl^- are commonly measured in urine so the other charged species are the unmeasured anions (UA) and cations (UC).
Because of the requirement for macroscopic electroneutrality, total anion charge always equals total cation charge, so:

Cl- + UA = Na⁺ + K⁺ + UC

Rearranging:

Urinary Anion Gap = ( UA - UC ) = [Na⁺]+ [K⁺] - [Cl^-]

Clinical Use

Key Fact: The urinary anion gap can help to differentiate between GIT and renal causes of a hyperchloraemic metabolic acidosis.

It has been found experimentally that the Urinary Anion Gap (UAG) provides a rough index of urinary ammonium excretion. Ammonium is positively charged so a rise in its urinary concentration (ie increased unmeasured cations) will cause a fall in UAG

Acid Base Learner Series: The Delta Ratio

Definition

This Delta Ratio is sometimes useful in the assessment of metabolic acidosis. As this concept is related to the anion gap (AG) and buffering, it will be discussed here before a discussion of metabolic acidosis. The Delta Ratio is defined as:

Delta ratio = (Increase in Anion Gap / Decrease in bicarbonate)

Others have used the delta gap (defined as rise in AG minus the fall in bicarbonate), but this uses the same information as the delta ratio and has does not offer any advantage over it.

How is this useful?

In order to understand this, consider the following:
If one molecule of metabolic acid (HA) is added to the ECF and dissociates, the one H⁺ released will react with one molecule of HCO₃^- to produce CO₂ and H₂O. This is the process of buffering. The net effect will be an increase in unmeasured anions by the one acid anion A^- (ie anion gap increases by one) and a decrease in the bicarbonate by one.
Now, if all the acid dissociated in the ECF and all the buffering was by bicarbonate, then the increase in the AG should be equal to the decrease in bicarbonate so the

Acid Base Learner Series: The Anion Gap

The Anion Gap: A balance 

Definition & Clinical Use

The term anion gap (AG) represents the concentration of all the unmeasured anions in the plasma. The negatively charged proteins account for about 10% of plasma anions and make up the majority of the unmeasured anion represented by the anion gap under normal circumstances. The acid anions (eg lactate, acetoacetate, sulphate) produced during a metabolic acidosis are not measured as part of the usual laboratory biochemical profile. The H⁺ produced reacts with bicarbonate anions (buffering) and the CO₂ produced is excreted via the lungs (respiratory compensation). The net effect is a decrease in the concentration of measured anions (ie HCO₃) and an increase in the concentration of unmeasured anions (the acid anions) so the anion gap increases.
AG is calculated from the following formula:

Anion gap = [Na⁺] - [Cl^-] - [HCO₃^-]

Reference range is 8 to 16 mmol/l. An alternative formula which includes K⁺ is sometimes used particularly by Nephrologists. In Renal Units, K⁺ can vary over a wider range and have more effect on the measured Anion Gap. This alternative formula is:

AG = [Na⁺] + [K⁺] - [Cl^-] - [HCO₃^-]

The reference range is slightly higher with this

Acid base balance: A complete explanation for Students, postgraduate Physicians especially Anesthesia Students

Definitions

The definitions of the terms used here to describe acid-base disorders are those suggested by the Ad-Hoc Committee of the New York Academy of Sciences in 1965. Though this is over 35 years ago, the definitions and discussion remain valid today.

Basic Definitions

• Acidosis - an abnormal process or condition which would lower arterial pH if there were no secondary changes in response to the primary aetiological factor.
• Alkalosis - an abnormal process or condition which would raise arterial pH if there were no secondary changes in response to the primary aetiological factor.
• Simple (Acid-Base) Disorders  are those in which there is a single primary aetiological acid-base disorder.
• Mixed (acid-Base) Disorders are those in which two or more primary aetiological disorders are present simultaneously.
• Acidaemia - Arterial pH < 7.36 (ie [H⁺] > 44 nM )
• Alkalaemia - Arterial pH > 7.44 (ie [H⁺] < 36 nM )

An acidaemia of course must be due to an acidosis so is an indicator of the presence of this disorder. In mixed acid-base disorders, there may be co-existing disorders each having opposite effects on the ECF pH so a quick check of the arterial pH is insufficient to fully indicate all primary acid-base disorders. In mixed disorders, it does indicate in general terms the most severe disorder. That is, if the arterial pH is 7.2 (an acidaemia), there must be an acidosis present, and any alkalosis present must be of lesser magnitude. (This idea is the basis of an initial step in the systematic approach to analysis of arterial blood gas results).

The Disorders

The 4 simple acid base disorders are:

• Respiratory acidosis
• Respiratory alkalosis
• Metabolic acidosis
• Metabolic alkalosis.

Respiratory disorders are caused by abnormal processes which tend to alter pH because of a primary change in pCO₂ levels.
Metabolic disorders are caused by abnormal processes which tend to alter pH because of a primary change in [HCO₃^-].

Correct Termin

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Pediatrics Saudi Licensing exam Questions for practice

Pediatrics Saudi Licensing exam Questions

The correct answers -as I hope- is clear by (T) sign. When you notice any wrong answer, tell me with your reference or discussion, please, so we can update to help others.

1. Mother brought her 18 month old infant to ER with history of URTI for the last 2 days with mild respiratory distress. This evening the infant start to have hard barking cough with respiratory distress. O/E: T 38C, RR 40/min, associated with nasal flaring, suprasternal & intercostal recessions. Auscultation to the chest shows equal air entry bilaterally, prolonged expiratory phase, and crackles. What is the most likely diagnosis?
a. Viral Pneumonia
b. Bacterial Pneumonia
c. Bronchiolitis
d. Acute epiglottitis
e. Trachiobronchiolitis ( T )

2. A 3 years old child woke from sleep with croup, the differential diagnosis should include all except:
a. Pneumonia ( T )
b. Tonsillitis
c. Cystic fibrosis
d. Airway foreign body
e. bronchial asthma

3. Regarding treatment of CROUP, All are TRUE EXCEPT:
a. IV fluids
b. Humidified oxygen
c. Sedative ( T )
d. Racemic epinephrine
e. Corticosteroid

4. An 8 months infant came complaining of croup, coryza, air trapping, tachy

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