Pathophysiology of obesity and starvation

1. NUTRITIONAL
DISEASES
RVS CHAITANYA
KOPPALA

2. OBESITY
Dietary imbalance and overnutrition may lead to
diseases like obesity.
O be sity is de fine d as an e xce ss o f adipo se tissue that
im parts he alth risk; a bo dy we ig ht o f 20 % e xce ss o ve r
ide alwe ig ht fo r ag e , se x and he ig ht is co nside re d a
he alth risk.
The m o st wide ly used method to gauge obesity is
body mass index (BMI)
 which is equal to weight in kg/height . A cut off BMI
value of 30 is used for obesity in both men and women

3. ETIOLOGY
Obesityresults whencaloric intakeexceeds utilisation. The
imbalance of these two components can occur in the following
situations:
1. Inade q uate pushing o f o ne se lf away fro m the dining table
causing overeating.
2. Insufficie nt pushing o f o ne se lf o ut o f the chair le ading to
inactivity and sedentary life style.
3. Ge ne tic pre dispo sitio n to de ve lo p o be sity.
4. Die ts larg e ly de rive d fro m carbo hydrate s and fats than
protein-rich diet.
5. Se co ndary o be sity m ay re sult fo llo wing a num be r o f
unde rlying diseases such as hypothyroidism, Cushing’s
disease, insulinoma and hypothalamic disorders.

4. PATHOGENESIS.
The lipid storing cells, adipocytes comprise the adipose
tissue, and are present in vascular and stromal compartment in
the body.
Besides the generally accepted role of adipocytes for fat
storage, these cells also release endocrine-regulating
molecules.
These molecules include:
Energy regulatory hormone (leptin),
Cytokines (TNF-a and interleukin-6),
Insulin sensitivity regulating agents (adiponectin, resistin and
RBP4),
Prothrombotic factors (plasminogen activator inhibitor),
Blood pressure regulating agent (angiotensingen).

5. Adipose mass is increased due to enlargement of adipose
cells due to excess of intracellular lipid deposition as well as
due to increase in the number of adipocytes.
The most important environmental factor of excess
consumption of nutrients can lead to obesity.
However, underlying molecular mechanisms of obesity are
beginning to unfold based on observations that obesity is
familial and is seen in identical twins.
Recently, two obesity genes have been found:
o b g e ne and its protein product leptin
db g e ne and its pro te in product leptin receptor.

6. SEQUELAE OF OBESITY.
Marked obesity is a serious
health hazard and may
predispose to a number of
clinical disorders and
pathological changes described
in give figure to the right

7. METABOLIC CHANGES.
These are as under:
1. Hyperinsulinaemia. Increased insulin secretion is a feature of
obesity. Many obese individuals exhibit hyperglycaemia or frank
diabetes despite hyperinsulinaemia. This is due to a state of insulin-
resistance consequent to tissue retention, hypoxia, polycythaemia and
eventually right-sided insensitivity.
2. Type 2 diabetes mellitus. There is a strong association of type
2 diabetes mellitus with obesity. Obesity often exacerbates the
diabetic state and in many cases weight reduction often leads to
amelioration of diabetes.
3. Hypertension. A strong association between hypertension and
obesity is observed. Weight reduction leads to significant reduction in
systolic blood pressure.

8. 4. Hyperlipoproteinaemia. The plasma cholesterol circulates in
the blood as low-density lipoprotein (LDL) containing most of the
circulating triglycerides. Obesity is strongly associated with VLDL
and mildly with LDL. Total blood cholesterol levels are also elevated
in obesity.
5. Atherosclerosis. Obesity predisposes to development of
atherosclerosis. As a result of atherosclerosis and hypertension,
there is increased risk of myocardial infarction and stroke in obese
individuals.
6. Nonalcoholic fatty liver disease (NAFLD). Obesity
contributes to development of NAFLD which may progress further to
cirrhosis of the liver.
7. Cholelithiasis. There is six times higher incidence of
gallstones in obese persons, mainly due to increased total body

9. 8. Hypoventilation syndrome (Pickwickian syndrome).
This is characterised by hypersomnolence, both at night and
during day in obese individuals along with carbon dioxide
retention, hypoxia, polycythaemia and eventually right-sided
heart failure.
9. Osteoarthritis. These individuals are more prone to
develop degenerative joint disease due to wear and tear
following trauma to joints as a result of large body weight.
10. Cancer. Diet rich in fats, particularly derived from animal
fats and meats, is associated with higher incidence of cancers
of colon, breast, endometrium and prostate

10. STARVATION
Starvation is a state of overall deprivation of nutrients. Its causes
may be the following:
Deliberate fasting—religious or political;
Famine conditions in a country or community; or
Secondary undernutrition such as due to chronic wasting diseases
(infections, inflammatory conditions, liver disease), cancer etc.
Cancer results in malignant cachexia as a result of which
cytokines are elaborated e.g. tumour necrosis factora, elastases,
proteases etc.
A starved individual has lax, dry skin, wasted muscles and
atrophy of internal organs.

11. METABOLIC CHANGES
The following metabolic changes take place in starvation:
1. Glucose.
Glucose stores of the body are sufficient for one day’s metabolic
needs only.
During fasting state, insulin independent tissues such as the brain,
blood cells and renal medulla continue to utilize glucose while
insulin-dependent tissues like muscle stop taking up glucose.
This results in release of glycogen stores of the liver to maintain
normal blood glucose level.
Subsequently, hepatic gluconeogenesis from other sources such

12. 2. Proteins.
Protein stores and the triglycerides of adipose tissue have
enough energy for about 3 months in an individual.
Pro te ins bre akdo wn to re le ase am ino acids which are used as
fuel for hepatic gluconeogenesis so as to maintain glucose
needs of the brain.
 This results in nitrogen imbalance due to excretion of
nitrogen compounds as urea.

13. 3. Fats.
After about one week of starvation
protein breakdown is decreased while trig lyce ride s o f
adipo se tissue breakdown to form glycerol and fatty acids.
The fatty acids are converted into ketone bodies in the liver
which are used by most organs including brain in place of
glucose.
Starvation can then continue till all the body fat stores are
exhausted following which death occurs.

14. PROTEIN-ENERGY
MALNUTRITION
The inadequate consumption of protein and energy as a result of
primary dietary deficiency or conditioned deficiency may cause loss
of body mass and adipose tissue,
Resulting in protein energy or protein calorie malnutrition (PEM or
PCM).
The primary deficiency is more frequent due to socioeconomic
factors limiting the quantity and quality of dietary intake,
Particularly prevalent in the developing countries of Africa, Asia
and South America.

15. The spectrum of clinicalsyndro m e s pro duce d as a
re sult of PEM includes the following
1 . Kwashiorkorwhich is re late d to pro te in de ficie ncy tho ug h
calorie intake may be sufficient.
2. Marasmus is starvatio n in infants o ccurring due to o ve rall
lack of calories.

16. THE SALIENT FEATURES OF THE TWO
CONDITIONS ARE CONTRASTED