nmda321 sn06 lecture acid base balance physiology revision –10 minute video on acid base balance: ...

NMDA321Nutritional Physiology Research

www.endeavour.edu.au

Session 6

Acid Base Balance

Nutritional Medicine Department

© Endeavour College of Natural Health www.endeavour.edu.au 2

Session 6

o Investigate the mechanisms and relationships to

disease processes and exploration of current clinical

research regarding:

o Acid Base balance

o Nutritional implications


Pre-reading

o Schwalfenberg, G.K., 2012. The alkaline diet: Is there evidence that

an alkaline pH diet benefits health? Journal of Environmental and

Public Health, 2012. Available at:

https://login.ezproxy.endeavour.edu.au:2443/login?url=http://search.

ebscohost.com/login.aspx?direct=true&db=mdc&AN=22013455&sit

e=eds-live&scope=site.

o Adeva, M.M. & Souto, G., 2011. Diet-induced metabolic acidosis.

Clinical Nutrition, 30(4), pp.416–421. Available at:

https://login.ezproxy.endeavour.edu.au:2443/login?url=http://search.

ebscohost.com/login.aspx?direct=true&db=edsgao&AN=edsgcl.262

897144&site=eds-live&scope=site

o Physiology revision – 10 minute video on acid base balance:

https://www.youtube.com/watch?v=i_pTaTveCCo

https://login.ezproxy.endeavour.edu.au:2443/login?url=http://search.ebscohost.com/login.aspx?direct=true&db=mdc&AN=22013455&site=eds-live&scope=site

https://login.ezproxy.endeavour.edu.au:2443/login?url=http://search.ebscohost.com/login.aspx?direct=true&db=edsgao&AN=edsgcl.262897144&site=eds-live&scope=site

https://www.youtube.com/watch?v=i_pTaTveCCo


Acids and Baseso Acids and bases are defined by their behaviour in water

(aqueous solution)

o Acid = a chemical that dissociates, releasing a hydrogen

ion (proton, H+) into solution

o Base = a chemical that produces negative ions in

solution which can then accept an acidic proton

Acid ↔ Base + H+

o The pH Scale: based on [H+] in a solution.

o Lower pH – more acidic; Higher pH – more basic or

alkaline; pH 7 - neutral


The pH Scale

Source: Fundamentals of Anatomy &

Physiology (9th Edition), 2011, Frederic H.

Martini et al.


Body pH

o Normal pH of the blood is tightly controlled in healthy

people. Range: 7.35 – 7.45

o The pH in other parts of the body varies considerably

(Schwalfenberg, 2012, p. 2)


Buffers

o Buffer = a chemical which resists a change in the pH of

a system

o The human body has systems that buffer or remove

excess acids and alkalis – to minimise pH change

o Bicarbonate is the major buffering system in body;

uses carbonic acid, which is created by dissolving CO2

in water

CO2 + H2O ↔ CH2CO3 ↔ H+ + HCO3-

(Carbon dioxide + water ↔ Carbonic acid ↔ hydrogen ion

+ bicarbonate)


Acid base homeostasis

o Many biochemical reactions of metabolism either

produce or consume acids and bases (Poupin et al 2012)

o As part of metabolism, the body generates volatile acid,

which is excreted as CO2 in the lungs, and non-volatile

acid, which is excreted by the kidney. (Yenchek et al 2014)

o The body buffers the impact of significant endogenous

acid production via the blood, lungs and kidneys


Image source:

https://au.pinterest.com/pin/32510428535865880/


Overview of Acid-Base Balance

The Merck Manual (Professional Version) –

comprehensive reference resource:

o Acid-Base Regulation

o Acid-Base Disorders

o http://www.merckmanuals.com/professional/SearchResul

ts?query=Overview+of+Acid-

Base+Balance&icd9=MM083%3bMM084

o OpenSTAX Anatomy and Physiology (free e-book)

Chapter 26

o https://openstax.org/details/anatomy-and-physiology

http://www.merckmanuals.com/professional/SearchResults?query=Overview+of+Acid-Base+Balance&icd9=MM083;MM084

https://openstax.org/details/anatomy-and-physiology


Minerals

Minerals leave an acidic or alkaline residue in the body

when metabolised

o Acid forming minerals: S, P, Cl (cations, –ve charge)

o Alkaline forming minerals: Ca, Mg, K, Na (anions, +ve

charge)

Image source:

http://sciencenotes.org/cat

egory/chemistry/periodic-

table-chemistry

http://sciencenotes.org/category/chemistry/periodic-table-chemistry


Acid-forming foods

o Meat, fish, chicken, eggs, grains (high in phosphate

which creates phosphoric acid)

o Animal proteins are rich in sulfur containing amino acids

cysteine and methionine (create sulfuric acid residues)

o Processed foods and soft drinks (phoshates used as

food additives)

o Salt (40% Na: 60% Cl) + 95% of Cl ions absorbed

causing a net increase in acid load

o Oxalate in food potentially acid forming but poorly

absorbed so unlikely to have much effect on body pH.

(Paxton 2015, p. 271; Adeva & Souto 2011; Welch et al 2008)


Alkaline-forming foods

o Foods that contain organic acids taste acidic (eg. citrus

fruit) but are not acid-forming because organic acids are

metabolised completely and produce bicarbonate

o Fruit, vegetables, nuts, legumes, in general, are alkaline

–forming

o Fruit & vegetables rich in potassium salts which form

bicarbonate as an end product

o Dairy products contain both acid-forming phosphate and

alkaline-forming calcium, and have a slight alkaline effect(Paxton 2015, p 271)

o Glutamate (anionic amino acid) consumes H+ when

metabolised to become neutral (Adeva & Souto 2011)


Acid/alkaline diets

o Most of the acids in the body are derived from sulphur

and phosphate in animal foods and grains, and chloride

from salt

o Most of the bicarbonate (alkali) is derived from organic

anions such as citrate provided by potassium salts in

fruits and vegetables

o Inadequate fruit and vegetable intake may lead to latent

acidosis and a reduction in the total buffering capacity of

the blood(Paxton 2015, p. 272; Adeva & Souto 2011)


Australian Diet Survey

o Results from 2011-12 Australian Diet Survey for

Australians aged 2 years and over

• 97% reported consuming cereals and grains

• 85% consumed dairy of which 32% had cheese

• 6.8% met the recommended intake of vegetables –

potatoes making up ¼ of what has been consumed.

• 54% met the recommendation for fruit

• 35% of total energy from discretionary foods – high in fat,

sugar, salt and alcohol

o ABS, 2014, 4364.0.55.007 - Australian Health Survey: Nutrition First Results - Foods

and Nutrients, 2011-12, available

here: http://www.abs.gov.au/ausstats/[email protected]/Lookup/4364.0.55.007main+features

12011-12

http://www.abs.gov.au/ausstats/[email protected]/Lookup/4364.0.55.007main+features12011-12


Diet-induced metabolic acidosis

o ‘Acidogenic diet’ urinary excretion of anions such as

sulfate, chloride and phosphate increases and there is

also urinary loss of calcium (Adeva & Souzo 2011)

o The kidneys are not able to excrete all of the acids

produced by modern diets chronic mild metabolic

acidosis (Paxton 2015, p. 272)

o “The daily net acid load’s magnitude (in part by

influencing systemic acid-base status) has been shown

to induce renal losses of calcium, magnesium and

nitrogen, and adversely affects numerous endocrine

functions.” (Frassetto et al 2007)


NEAP = Net Endogenous Acid

Productiono The outcome of acid-alkali interactions in the body –

closely reflects the dietary protein : potassium ratio (Paxton 2015, p. 272)

o “…the amount of net acid produced by the metabolic

system per day…, results predominately from

differences in the relative amounts of the diet’s acid load

and base precursors absorbed by the gut” (Frassetto et al

2007)

o “Diet-dependent acid load produced by the excessive

dietary content of acid precursors, approximately

estimated from renal net acid excretion” (Adeva & Souto

2011, p. 416)


PRAL = Potential Renal Acid

Loado Used to categorize foods based on the amounts of

alkalising minerals (Mg, K, Ca) and the chloride,

phosphate and protein content of each food

o Originally based on German research, then developed

by the USDA; considered by scientists to be the most

accurate way of measuring the dietary acid load on the

body

o PRAL reference list - Schwalfenberg 2012

• Negative values indicate alkalising effect; positive values

indicate acidic forming

• The lower the number the more alkaline, the higher the number,

the more acidic. Zero = neutral



Pathology testing

o Urine pH

• Lab Tests Online - Urine pH

o Electrolytes

• Lab Tests Online – Electrolytes

o Bicarbonate

• Lab Tests Online - Bicarbonate

o Anion gap

• Anion gap - Lab Tests Online

• The Merck Manual - The anion gap

o RACGP Manual

• https://www.rcpa.edu.au/Library/Practising-Pathology/RCPA-

Manual/Home

http://www.labtestsonline.org.au/learning/test-index/urinalysis#tab-index=1

https://labtestsonline.org/understanding/analytes/electrolytes/tab/test/

https://labtestsonline.org/understanding/analytes/co2/tab/test/

http://www.labtestsonline.org.au/learning/test-index/electrolytes#tab-index=3

http://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/acid-base-regulation-and-disorders/acid-base-disorders#v8329336

https://www.rcpa.edu.au/Library/Practising-Pathology/RCPA-Manual/Home


Urine pH

o Urine reflects key excretory path for metabolic acids,

therefore indicative of acidic burden and kidney’s ability

to compensate.

o Urine pH varies from acid to alkaline depending on the

need for balancing the internal environment (Schwalfenberg

2012)

o Dietary acid-base load is significantly related to urine pH.

A more alkaline urine is associated with a more alkaline

dietary load and vice versa.

o Urine pH provides a simple tangible measure of the

effects of diet and could be used to monitor change in

diet quality (Welch et al 2008)


Urine pH

o An acidic urine (pH < 5.5) has been established as an

accurate indicator of:

• Acidogenic diet

• Increased urinary calcium loss

• Accelerated progression of chronic kidney disease

• Increased risk of urate renal stone production

• Increased risk of cardiovascular and all cause mortality

• Increased risk of bladder cancer

o Urinary pH has also been shown to reflect increased

intake or alkaline foods


Bicarbonate (HCO3)

o Primary acid buffering system in the blood

o Levels are principally regulated by the kidney

o Serum bicarbonate is increased in metabolic alkalosis

and in compensated respiratory acidosis (RCPA manual)

o Typically demonstrates a direct relationship with pH:

Plasma levels Systemic pH Effect is:

↑ HCO3 ↑ pH Alkalising

↓ HCO3 ↓ pH Acidifying


Bicarbonate (HCO3)

o Lab Tests Online – Bicarbonate

o Reference range for adults: 23-29 mEq/L

o Suboptimal HCO3 (< 23) has been associated with:

• Acidogenic diets

• Accelerated progression of chronic kidney disease

• Reduced bone mineral density in post-menopausal women and

older men

• Increased rate of bone loss

• Impaired mobility and ‘incident functional limitation’ in the elderly

(Yenchek et al 2014)

• Increased risk of cardiovascular and all cause mortality (Park et

al 2015)

https://labtestsonline.org/understanding/analytes/co2/


Causes of low bicarbonate

1. Increased use – acid buffering

a) Metabolic acidosis

b) Starvation

c) Diabetes (poorly controlled)

2. Increased losses – renal and/or GIT

a) Diarrhoea

b) Kidney damage

c) Chronic use of loop diuretics

3. Medications

• Phenformin, tetracycline, methicillin, nitrofurantoin, thiazide

diuretics, triamterene


Anion gap

o The anion gap is defined as serum sodium (Na)

concentration minus the sum of chloride (Cl−) and

bicarbonate (HCO3−) concentrations; Na+−(Cl−+HCO3

−)

(The Merck Manual). Sometimes includes potassium (K)

o The difference between the concentration of measured

cations and anions in plasma = Na (+/- K) – (Cl & HCO3)

Anion Gap = Other unmeasured

anions (eg. PO4, SO4,

lactate, etc.)

↑ Anion Gap = ↑ Acidity


Anion gap

o Lab Tests Online - Anion gap

o Increased levels (> 12mEq/L if including K, > 8 if not)

• Acidogenic diet and lifestyle

• Lactic acidosis

• Diabetic or alcoholic ketoacidosis

• Increased HCO3 losses from GIT (eg. diarrhoea, IBD)

• Impaired ability to produce HCO3

• Renal impairment and renal failure

• Medications, ethanol

o Decreased levels (< 8mEq/L if including K, < 4 if not)

• Excessive antacid use

• Chronic vomiting

https://labtestsonline.org/understanding/analytes/electrolytes/tab/faq


Effects of Acidosis(causative or compounding)

o Reduced energy –

disrupts ATP

production

o Free radicals and

oxidative damage

o Kidney

disease/stones

o Loss of minerals from

bone – osteopenia

and osteoporosis

o Sarcopenia

o Inflammation

o Insulin resistance

o Impacts stress

response – activated

HPA axis

o Hypertension

o Gout

o Pain/lower back pain


The straight line hypothesis of

diet, acidosis and aging

Image source: Berkemeyer 2009


Effects of acidosis on the boneo BONE = largest reserve of alkali in the body

o In acidosis, osteoclast activity increased and osteoblast

activity inhibited; bones release bicarbonate, K, Na, Ca,

Mg to buffer acidity

o Bicarbonate is excreted and reabsorbed by the kidneys

to maintain stable pH and electrical neutrality

o Muscle is broken down to produce ammonia (strongly

alkaline) + kidneys increase excretion of acids

o The kidneys cannot excrete urine more acid than pH 4.4

excess acids are buffered by forming complexes with

minerals (K, Ca, Mg) – leading to mineral losses in the

urine

(Paxton 2015, p. 272)


Effects of acidosis on the boneAdeva & Souzo 2011

o Increased rates of endogenous acid production are

associated with reduced kidney tubule calcium

reabsorption resulting in hypercalciuria and negative

calcium balance

o Urinary calcium excretion is higher in animal protein diet

compared to vegetarian diet

o Urinary calcium excretion falls as fruit and vegetable

(F&V) ingestion rises calcium retaining effect +

predictor of greater bone density in postmenopausal

women & healthy children

o Dietary depletion of F&V induces hypercalciuria



Osteoporosis and diet

o Fenton et al 2011

o No support found for “acid-ash” hypothesis: “acid”

modern diet causes osteoporosis & alkaline diet or

supplements prevent osteoporosis

o Hanley & Whiting 2013

o Confirmed not enough evidence to support causal

relationship between the acid/alkali composition of diet

and bone health

o Urinary calcium loss does not necessarily mean a

negative calcium balance or bone loss

o Beneficial role for bone metabolism of diet high in F&V


https://www.researchgate.net/publication/257461170_Does_a_High_Dietary_Acid_Content_Cause_Bone_Loss_and_Can_Bone_Loss_Be_Prevented_With_an_Alkaline_Diet


Effects of acidosis on the

kidneys

o Diet-induced metabolic acidosis promotes low urine pH,

hypercalciuria and hypocitraturia, predisposing to uric

acid and calcium kidney stone formation (nephrolithiasis)

o Low urine pH – major risk factor for uric acid stone

formation

o Functional changes take place in the kidney: increased

renal plasma flow and glomerular filtration rate – to

remove excess acid load kidney hypertrophy(Adeva & Souto 2011)


Urine pH and uric acid

Kanbara et al 2012

o Small crossover study – 18 female healthy university

students – ‘acidic’ vs ‘alkaline’ diet

o Uric acid in the serum was higher in the acidic group

than in the alkaline group

o Uric acid in the urine was lower for the acidic group than

in the alkaline group

o Uric acid may be reabsorbed more actively in acidic

urine than in alkaline urine

o Concluded that alkalization of urine by eating alkaline

diet is effective for removing uric acid from the body



The effect of aging on the kidney

o With aging, there is a decreased ability of the kidneys to

excrete an acid load.

o Low bicarbonate levels might reflect occult tubular

dysfunction, leading to acid retention, or an increased

acid load that is greater than the aging kidney’s ability to

excrete the load. (Yenchek et al 2014)


Acid-base balance & Sarcopenia

Yenchek et al 2014

o Acidosis can produce muscle catabolism, leading to

decreased muscle mass and decreased lower extremity

strength

o Acidosis leads to impaired insulin/IGF signalling; this

leads to upregulation of proteolytic pathways in muscle

muscle wasting

o Low serum bicarbonate (< 23 mEq/L) was associated

with slower gait speed, less quadriceps strength, and

subsequent development of impaired physical

functioning in previously well functioning older adults.

https://login.ezproxy.endeavour.edu.au:2443/login?url=http://search.ebscohost.com/login.aspx?direct=true&db=rzh&AN=109768356&site=eds-live&scope=site


Acid base balance and weight gain

Berkemeyer 2009

o Both under and over nutrition are conditions of catabolic

stress and related to the risk of developing acid retention

o The loss of muscle mass is made worse on a protein

deficient diet, even so protein adds to the acid load of

the body

o The correction of acidosis warrants urgent increased

consumption of vegetables and fruits and/or alkali

supplements. A regular consumption of these would

prevent the acidosis from setting in in the first place and

should be vigorously targeted as a health objective

o Breathing dynamics also important for maintaining acid

base balance (Berkeymeyer 2009)

https://login.ezproxy.endeavour.edu.au:2443/login?url=http://search.ebscohost.com/login.aspx?direct=true&db=edselp&AN=S0306987709002333&site=eds-live&scope=site


Image source: Berkemeyer 2009, p.354


Cardiovascular effects

Park et al 2015

o n = 31 590 healthy adults; median follow up 93 months

o An increase in daily metabolic acid load in the general

population with normal renal function is believed to result

from acidogenic modern diets.

o Clinical biomarkers of a higher metabolic acid load, such

as lower serum bicarbonate level and urine pH were

associated with a higher all-cause mortality

o This association was more prominent in participants with

BMI > 23

o Compared with serum bicarbonate and urine pH, serum

anion gap was not significantly associated with mortality



pH and Enzyme Function

o There are 75,000 enzymes in the human body; over

7000 metabolic processes depend on enzymes for

critical processes

o Enzyme activity affected by: temperature, genetic

variants, pH

o Each type of enzyme has optimum pH conditions. If the

pH changes from the optimum, the chemical nature of

the amino acids is altered reduced function of enzyme

o pH imbalance/acidity may affect vital enzymes such as:

• ATP synthase

• Glutathione peroxidase

• MTHFR (methyltetrahydrofolate reductase)

(Lewerenz et al 2010)


pH and the Microbiome

o Duncan et al 2009

o The pH of our digestive tract influences microbial

colonisation

o Latent acidity influences the pH of the mucosal terrain

which in turn affects bacterial growth and survivability

o Sensitivity to pH varies from one species of bacteria to

another. Most colonic bacteria generally grow well at

approx. pH 6.5

o “Inhibition of the growth of bacteria at mildly acidic pH

creates niches that can be exploited by more low-pH-

tolerant microorganisms” (Duncan et al 2009)



pH and the Microbiome

Colonic species composition

changes

At more acidic pH 5.5 or less

Firmicutes 50% reduction in growth

Bacteriodes Grew very poorly (or no growth)

Beneficial E. Coli strains Very poor growth rate

Butyrate producing species Significantly reduced

Bifidobacterium Some species grew better than others

Colonic pH varies depending on dietary intake, mucosal

terrain (host secretions) and fermentation end products of

gut microorganisms (Duncan et al 2009)


The primary benefits that may result from

adherence to Alkaline Diet are:

o Increased fruits and vegetables in an alkaline diet would

improve potassium/sodium ratio and may benefit bone

health, reduce muscle wasting, as well as mitigate other

chronic diseases such as hypertension and strokes .

o In increase in growth hormone with an alkaline diet may

improve many outcomes from cardiovascular health to

cognition and memory .

o An increased in intracellular magnesium, necessary for

energy metabolism and the function of many enzymes is

another benefit for an alkaline diet. Furthermore,

magnesium is necessary to activate vitamin D and

therefore this is another potential mechanism for

improved bone health .


The primary benefits that may result from

adherence to Alkaline Diet are:

o Alkaline diet improves uric acid clearance offering

protection against the development of gout, diabetes,

metabolic syndrome and hypertension.

o Reduces cumulative mild metabolic acidosis associated

with ageing reducing calcium excretion, bone resorption

markers and osteoporotic risk.


Referenceso Adeva, M.M. & Souto, G., 2011. Diet-induced metabolic acidosis. Clinical Nutrition,

30(4), pp.416–421. Available at:

https://login.ezproxy.endeavour.edu.au:2443/login?url=http://search.ebscohost.com/lo

gin.aspx?direct=true&db=edsgao&AN=edsgcl.262897144&site=eds-live&scope=site.

o Berkemeyer, S., 2009. Acid-base balance and weight gain: Are there crucial links via

protein and organic acids in understanding obesity? Medical Hypotheses, 73(3),

pp.347–356. Available at:


gin.aspx?direct=true&db=edselp&AN=S0306987709002333&site=eds-

live&scope=site.

o Duncan, S.H. et al., 2009. The role of pH in determining the species composition of

the human colonic microbiota. Environmental Microbiology, 11(8), pp.2112–2122.

Available at:



o Fenton, T.R. et al., 2011. Causal assessment of dietary acid load and bone disease: a

systematic review & meta-analysis applying Hill’s epidemiologic criteria for causality.

Nutrition journal, 10(1), p.41. Available at:




https://login.ezproxy.endeavour.edu.au:2443/login?url=http://search.ebscohost.com/login.aspx?direct=true&db=edselp&AN=S0306987709002333&site=eds-live&scope=site




Referenceso Hanley, D.A. & Whiting, S.J., 2013. Does a High Dietary Acid Content Cause Bone

Loss, and Can Bone Loss Be Prevented With an Alkaline Diet? Journal of Clinical

Densitometry.

o Kanbara, A. et al., 2012. Effect of urine pH changed by dietary intervention on uric

acid clearance mechanism of pH-dependent excretion of urinary uric acid. Nutrition

Journal, 11(1), p.39. Available at:


gin.aspx?direct=true&db=edsgao&AN=edsgcl.297993473&site=eds-live&scope=site

o Lewerenz, J., Dargusch, R. & Maher, P., 2010. Lactacidosis modulates glutathione

metabolism and oxidative glutamate toxicity. Journal of Neurochemistry, 113(2),

pp.502–514. Available at:


gin.aspx?direct=true&db=aph&AN=48598965&site=eds-live&scope=site.

o Park, M. et al., 2015. Association between the markers of metabolic acid load and

higher all-cause and cardiovascular mortality in a general population with preserved

renal function. Hypertension research, 38(6), pp.433–438. Available at:


gin.aspx?direct=true&db=mdc&AN=25762414&site=eds-live&scope=site.

o Paxton, F., 2015. Foundations of Naturopathic Nutrition, Sydney: Allen & Unwin.


https://login.ezproxy.endeavour.edu.au:2443/login?url=http://search.ebscohost.com/login.aspx?direct=true&db=aph&AN=48598965&site=eds-live&scope=site



Referenceso Poupin, N. et al., 2012. Impact of the diet on net endogenous acid production and

acid-base balance. Clinical Nutrition, 31(3), pp.313–321. Available at:



o Schwalfenberg, G.K., 2012. The alkaline diet: Is there evidence that an alkaline pH

diet benefits health? Journal of Environmental and Public Health, 2012. Available at:


gin.aspx?direct=true&db=mdc&AN=22013455&site=eds-live&scope=site.

o Welch, A. a et al., 2008. Urine pH is an indicator of dietary acid-base load, fruit and

vegetables and meat intakes: results from the European Prospective Investigation

into Cancer and Nutrition (EPIC)-Norfolk population study. The British journal of

nutrition, 99(6), pp.1335–1343. Available at:

http://search.proquest.com.ezproxy.endeavour.edu.au/health/docview/213830182?ac

countid=45102.

o Yenchek, R. et al., 2014. Association of serum bicarbonate with incident functional

limitation in older adults. Clinical Journal of the American Society of Nephrology,

9(12), pp.2111–2116. Available at:


gin.aspx?direct=true&db=rzh&AN=109768356&site=eds-live&scope=site.



http://search.proquest.com.ezproxy.endeavour.edu.au/health/docview/213830182?accountid=45102

https://login.ezproxy.endeavour.edu.au:2443/login?url=http://search.ebscohost.com/login.aspx?direct=true&db=rzh&AN=109768356&site=eds-live&scope=site

nmda321 sn06 lecture acid base balance physiology revision –10 minute video on acid base balance: ...

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