PROTEIN ENERGY MALNUTRITION AND

GOUT

Z Ngwira
 HUMAN NUTRITION
• Nutrients are substances that are crucial for
human life, growth & well-being.
• Macronutrients (carbohydrates, lipids,
proteins ) are needed for energy and cell
multiplication & repair.
• Micronutrients are trace elements &
vitamins, which are essential for metabolic
processes.
 HUMAN NUTRITION CONT..
• Obesity & under-nutrition are the 2 ends of
the spectrum of malnutrition.
• A healthy diet provides balanced nutrients
that satisfy the metabolic needs of the body
without excess or shortage.
• Dietary requirements of children vary
according to age, sex & development.
 Assessment of Nutr status

• Direct
– Clinical
– Anthropometric
– Dietary
– Laboratory
• Indirect
– Health statistics
– Ecological variables
 Clinical Assessment

• Useful in severe forms of PEM

• Based on thorough physical examination for
features of PEM & vitamin deficiencies.
• Focuses on skin, eye, hair, mouth & bones.
• Chronic illnesses & goiter to be excluded
 Clinical Assessment CONT..

• ADVANTAGES
– Fast & Easy to perform
– Inexpensive
– Non-invasive
• LIMITATIONS
– Does not detect early cases
– Trained staff needed
 ANTHROPOMETRY

• Objective with high specificity & sensitivity

• Measuring Ht, Wt, MAC, HC, skin fold
thickness, waist & hip ratio & BMI
• Reading are numerical & gradable on
standard growth charts
• Non-expensive & need minimal training
 ANTHROPOMETRY cont..

• LIMITATIONS
– Observers’ errors in measurement
– Limited nutritional diagnosis
– Problems with reference standards
– Arbitrary statistical cut-off levels for
abnormality
 LAB ASSESSMENT

• Biochemical
– Serum proteins, creatinine/hydroxyproline
• Hematological
– FBC, iron, vitamin levels
• Microbiology
– Parasites/infection
 DIETARY ASSESSMENT

• Breast & complementary feeding details

• 24 hr dietary recall
• Home visits
• Calculation of protein & Calorie content of
children foods.
• Feeding technique & food habits
 OVERVIEW OF PEM
• The majority of world’s children live in
developing countries
• Lack of food & clean water, poor sanitation,
infection & social unrest lead to LBW & PEM
• Malnutrition is implicated in >50% of deaths
of <5 children (5 million/yr)
 PEM in Sub-Saharan Africa
• PEM in Africa is related to:
– The high birth rate
– Subsistence farming
– Overused soil, drought & desertification
– Pests & diseases destroy crops
– Poverty
– Low protein diet
– Political instability (war & displacement)
PRECIPITATING FACTORS

 LACK OF FOOD (famine, poverty)

 INADEQUATE BREAST FEEDING

 WRONG CONCEPTS ABOUT NUTRITION

 DIARRHOEA & MALABSORPTION

 INFECTIONS (worms, measles, T.B)

 CLASSIFICATION

– A. (Welcome Trust Working Party

diagnostic criteria)
– Parameter: weight for age + oedema
– Grades:
• 60-80 % without oedema is under weight
• 60-80% with oedema is Kwashiorkor
• < 60 % with oedema is Marasmus-Kwash
• < 60 % without oedema is Marasmus
CLASSIFICATION cont..

– B. COMMUNITY (GOMEZ)
– Parameter: weight for age
– Grades:
•I (Mild): 90-70 percent
• II (Moderate): 70-60 percent
• III (Severe) : < 60 percent
 ADVANTAGES

 SIMPLICITY (no lab tests needed)

 REPRODUCIBILITY
 COMPARABILITY
 ANTHROPOMETRY+CLINICAL SIGN USED
FOR ASSESSMENT
 DISADVANTAGES

 AGE MAY NOT BE KNOWN

 HEIGHT NOT CONSIDERED
 CROSS SECTIONAL
 CAN’T TELL ABOUT CHRONICITY
 WHO STANDARDS MAY NOT REPRESENT
LOCAL COMMUNITY STANDARD
 KWASHIORKOR
• Cecilly Williams, a British nurse, had
introduced the word Kwashiorkor to the
medical literature in 1933. The word is taken
from the Ga language in Ghana & used to
describe the sickness of weaning.
 AETIOLOGY

• Kwashiorkor can occur in infancy but its

maximal incidence is in the 2nd yr of life
following abrupt weaning.
• Kwashiorkor is not only dietary in origin.
Infective, psycho-social, and cultural factors
are also operative.
 AETIOLOGY cont..
• Kwashiorkor is an example of lack of
physiological adaptation to unbalanced
deficiency where the body utilized proteins
and conserve subcutaneous fat.
• One theory says Kwash is a result of liver injury
with hypoproteinemia and oedema. Food
toxins like aflatoxins have been suggested as
precipitating factors.
 CLINICAL PRESENTATION
• Kwash is characterized by certain constant
features in addition to a variable spectrum of
symptoms and signs.
• Clinical presentation is affected by:
• The degree of deficiency
• The duration of deficiency
 The speed of onset
 The age at onset
 Genetic factors
CONSTANT FEATURES OF KWASH

• OEDEMA

• PSYCHOMOTOR CHANGES

• GROWTH RETARDATION

• MUSCLE WASTING
USUALLY PRESENT SIGNS

• MOON FACE

• HAIR CHANGES

• SKIN DEPIGMENTATION

• ANAEMIA
OCCASIONALLY PRESENT SIGNS

• HEPATOMEGALY
• FLAKY PAINT DERMATITIS
• CARDIOMYOPATHY & FAILURE
• DEHYDRATION (Diarrh. & Vomiting)
• SIGNS OF VITAMIN DEFICIENCIES
• SIGNS OF INFECTIONS
 MARASMUS
• The term marasmus is derived from the
Greek marasmos, which means wasting.
• Marasmus involves inadequate intake of
protein and calories and is characterized by
emaciation.
• Marasmus represents the end result of
starvation where both proteins and calories
are deficient.
 MARASMUS cont..

• Marasmus represents an adaptive response

to starvation, whereas kwashiorkor
represents a fed state.
• In Marasmus the body utilizes all fat stores
before using muscles.
EPIDEMIOLOGY & AETIOLOGY

• Seen most commonly in the first year of life

due to lack of breast feeding and the use of
dilute animal milk.
• Poverty or famine and diarrhoea are the
usual precipitating factors
• Ignorance & poor maternal nutrition are also
contributory
Clinical Features of Marasmus

• Severe wasting of muscle & s/c fats

• Severe growth retardation
• Child looks older than his age
• No oedema or hair changes
• Alert but miserable
• Hungry
• Diarrhoea & Dehydration
 CLINICAL ASSESSMENT

• Interview & physical exam including detailed

dietary history.
• Anthropometric measurements
• Team approach with involvement of
dieticians, social workers & community
support groups.
 Investigations for PEM
• Full blood counts
• Blood glucose profile
• Septic screening
• Stool & urine for parasites & germs
• Electrolytes, Ca, Ph & ALP, serum proteins
• Exclude HIV & malabsorption
 Complications of P.E.M
• Hypoglycemia
• Hypothermia
• Hypokalemia
• Hyponatremia
• Heart failure
• Dehydration & shock
• Infections (bacterial, viral & thrush)
 TREATMENT

• Correction of water & electrolyte imbalance

• Treat infection & worm infestations
• Dietary support: 3-4 g protein & 200 Cal /kg body
wt/day + vitamins & minerals
• Prevention of hypothermia
• Counsel parents & plan future care including
immunization & diet supplements
 KEY POINT FEEDING

• Continue breast feeding

• Add frequent small feeds
• Use liquid diet
• Give vitamin A & folic acid on admission
• With diarrhea use lactose-free or soya bean
formula
 PROGNOSIS

• Kwash & Marasmus-Kwash have greater risk

of morbidity & mortality compared to
Marasmus and under weight
• Early detection & adequate treatment are
associated with good outcome
• Late ill-effects on IQ, behavior & cognitive
functions are doubtful and not proven
Hyperuricaemia & Gout
 Overview
• Nucleic acids contain bases of two different
types, pyrimidines and purines.

• The catabolism of the purines, adenine and

guanine, produces uric acid.

• At physiological hydrogen ion concentration,

uric acid is mostly ionized and present in
plasma as sodium urate.
 Overview cont..
• An elevated serum urate concentration is known
as hyperuricaemia.

• Uric acid and sodium urate are relatively insoluble

molecules that readily precipitate out of aqueous
solutions such as urine or synovial fluid.

• The consequence of this is the medical condition

gout.
 Urate formation
• Urate is formed in three ways. These are:
by de novo synthesis (from phosphoribose, aas,
one carbon units & CO2 as raw materials to
synthesise purine nucleotides).

by the metabolism of endogenous DNA, RNA and

other purine-containing molecules such as ATP

by the breakdown of dietary nucleic acids.

 Urate excretion
• Urate is excreted in two ways:
1. Via the kidney.
 The majority of urate is excreted via the kidney.
 Renal handling of urate is complex.
 It is freely filtered at the glomerulus, but 99% is
reabsorbed in the proximal tubule.
 The distal tubules also secrete urate, but again
much is reabsorbed.
 The amount of urate excreted in the urine is
around 10% of that filtered at the glomerulus.
 Urate excretion cont..
2. Via the gut.
Smaller amounts of urate are excreted into
the gut where it is broken down by bacteria.

This process is called uricolysis.

 Uric acid metabolism
• Urate concentrations in serum are higher in men than
women.

• Even within the reference interval, serum urate is near

its aqueous solubility limit.

• The presence of protein helps to keep the molecule in

solution.

• A high serum urate may arise from increased urate

formation, or from decreased excretion.
 Uric acid metabolism cont..
• The common causes of hyperuricaemia are
summarized in Figure 72.3.

• Genetic causes of hyperuricaemia are known as

primary disorders, and there are also secondary
causes.

• Most primary causes are due to decreased

excretion of urate (90% of cases) rather than
increased production (10%).
 Lesch–Nyhan syndrome
• One genetic disorder that should be singled out is
Lesch– Nyhan syndrome, an X-linked disorder
caused by a deficiency of hypoxanthine-guanine
phosphoribosyltransferase, an enzyme that is
involved in salvaging purine bases for resynthesis
to purine nucleotides.

• The syndrome is characterized clinically by

excessive uric acid production, hyperuricaemia
and neurological problems that include self-
mutilation and mental retardation.
 Gout
• Gout is a clinical syndrome that is characterized
by hyperuricaemia and recurrent acute arthritis.

• Whereas all patients who develop gout will have

had hyperuricaemia at some point in the
development of the disease, only a minority of
patients with hyperuricaemia develop gout.

• The reason for this is not known.

 Gout cont..
• Acute gout is triggered by the tissue
deposition of sodium urate crystals that cause
an intense inflammatory response.

• In the chronic situation, tophaceous deposits

of sodium urate may form in the tissues (Fig
72.4).
 Gout cont..
• Gout is exacerbated by alcohol.

• The reason for this is twofold.

• Ethanol increases the turnover of ATP and urate

production.

• Ethanol in excess may cause the accumulation of

organic acids that compete with the tubular
secretion of uric acid.
 Gout cont..
• Disorders such as ethanol intoxication,
diabetic ketoacidosis and starvation lead to
elevations of lactic acid, β-hydroxybutyric acid
and acetoacetic acid, and will cause
hyperuricaemia.
 Treatment of Gout
• The symptoms of acute gout respond to anti-
inflammatory drugs such as indomethacin, but it
should be noted that these drugs have no direct
effect on the serum urate level.

• Low-dose aspirin should be avoided as it inhibits

renal urate excretion.

• Treatment must also be directed at the

hyperuricaemia.
 Treatment of Gout cont..
• Drugs such as probenecid, which promote urate
excretion, can be used prophylactically.

• A diet that is low in purines and alcohol may be

prescribed in an effort to reduce the plasma urate
concentration.

• Allopurinol, a specific inhibitor of the enzyme

xanthine oxidase that catalyses the oxidation of
hypoxanthine to xanthine and uric acid, may also
be effective in reducing urate concentrations.
 Treatment of Gout cont..
• A number of other crystalline arthropathies
may present as gout but are not associated
with hyperuricaemia (so-called pseudogout).

• Most notably, pseudogout is due to the

deposition of calcium pyrophosphate crystals.
Renal disease and hyperuricaemia
• Renal disease is a common complication of
hyperuricaemia.

• Several types of renal disease have been identified.

• The most common is urate nephropathy, which is

caused by the deposition of urate crystals in renal
tissue or the urinary tract to form urate stones.

• This may be associated with chronic hyperuricaemia.

 Renal disease and hyperuricaemia
cont..
• Acute renal failure can be caused by the rapid precipitation
of uric acid crystals that commonly occurs during treatment
of patients with leukaemias and lymphomas.

• nucleic acids are released as a result of tumour cell

breakdown, are rapidly metabolized to uric acid and this
sometimes results in very high concentrations, precipitating
gout or nephropathy.

• In these cases, urate oxidase is sometimes administered

prophylactically to metabolize the uric acid to allantoin,
which is safely excreted by the kidney.
 Urate in pregnancy
• Serum urate is of value in the monitoring of
maternal well-being in pregnancy associated
hypertension (pre-eclampsia), alongside other
markers such as blood pressure, urine protein
excretion and creatinine clearance
 Hypouricaemia
• Rare unless as a result of treatment of hyperuricaemia with,
for example, allopurinol or probenecid.

• It is associated with proximal renal tubular damage, in which

the reabsorption of urate is reduced, and can be seen in
Fanconʼs syndrome.

• Also seen in parenteral nutrition, pregnancy, SIADH, and

T1DM
 Xanthinuria
• A very rare inborn error of purine metabolism, inherited as
autosomal recessive disorder.

• There is a deficiency of xanthine oxidase in the liver.

• Purine breakdown stops at xanthine-hypoxanthine stage, and

plasma and urate levels are very low.

• Increased xanthine excretion may lead to formation of

xanthine stones.
 Summary
• Uric acid is formed from the breakdown of
endogenous or exogenous purines.

• Hyperuricaemia may be caused by:

 an increased rate of purine synthesis
 an increased rate of turnover of nucleic acids, as
in malignancies, tissue damage or starvation
 a reduced renal excretion.
 Summary cont..
• Hyperuricaemia is a risk factor for gout that
occurs when urate crystals are deposited in
tissues.

• Hyperuricaemia is aggravated by a diet high in

purines and alcohol.
THE END