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Dr.

Subhashinie Senadheera
Department of Biochemistry
Faculty of Medicine and Allied Sciences
Rajarata University of Sri Lanka
Objectives

Student should be able to,


• state the constituents of oral rehydration
solution (ORS) and their functions
• list alternate home remedies for ORS and
their advantages
• define the term malabsorption
• describe the causes of malabsorption
• describe the effects of malabsorption
Digestive disorders

• Impaired breakdown of nutrients in to


absorbable split products – Maldigestion
• Defective mucosal uptake and transport of
adequately digested nutrients –
malabsorption
• Malabsorption syndrome (MAS) – a clinical
term that encompasses defects occurring
during digestion and absorption
(1) Achlorhydria/ Hypochlorhydria
• A condition with an absent or low
production of gastric acid
• Intragastric pH >5.09 in men and > 6.81 in
women with peak acid output with
maximally effective stimulus
• Atrophic gastritis (AG) - atrophy of the corpus
mucosa leads to low synthesis of pepsinogen I
• Serum pepsinogen I : pepsinogen II ratio < 2.9
• Advanced gastric atrophy and hypo- or
achlorohydrias cause very low levels of
pepsinogen I in contrast to pepsinogen II, which
remains elevated in serum
Achlorhydria - Causes
• Autoimmune diseases: antibodies against
parietal cells and IF (pernicious anemia) 
atrophic gastritis
• Anti-secretory drugs: H2-receptor antagonists or
proton pump inhibitors (PPI)  long term use
• Helicobacter pylori infection (represses H-K-
ATPase alpha subunit gene expression)
• Gastric bypass surgery, radiation to stomach
• Hypothyroidism, VIPoma and gastric cancer
are also associated with achlorhydria
• A VIPoma is an endocrine tumor that
usually arises from beta-pancreatic cells
secreting vasoactive intestinal peptide (VIP)
• Leads to a syndrome of watery diarrhea,
hypokalemia, and achlorhydria (WDHA
syndrome)
Functions of Gastric Acid

• Supplies the acidic pH to the stomach (pH 1 –


2)
• Activation of pepsinogen to pepsin
• Helps to digest nutrients (i.e. denature and
alter the tertiary structure to ease digestion)
• Kill microbes present in ingested food/ drinks
Signs and symptoms

• Mild diarrhea
• Epigastric pain and bloating
• Weight loss
• Anaemia related signs and symptoms
(pernicious anaemia and iron def. anaemia)
Reasons…
• Impaired protein digestion by reduced / no
activation of pepsin
• Bacterial overgrowth
• Diarrhea or decreased absorption of
nutrients and vitamins, vitamin C, K & B
complex
• Malabsorption of basic electrolytes (Mg, Zn)
and vitamins
• Coexistent iron deficiency – achlorhydria??
achlorhydria prevents solubilization of
dietary ferric iron from food stuffs
Treatment

• Addressing the underlying cause of


symptoms

• Meal-time supplementation with


betaine hydrochloride (betaine-HCL)

• Minerals and vitamins (B12)


supplementation
(2) Intrinsic Factor (IF) Deficiency
Pernicious anemia

• An autoimmune disease
• Antibodies against IF/ parietal cells
• Causes vit B12 deficiency
GERD

• Gastroesophageal Reflux Disease (GERD) is


a digestive disorder
• Occurs when acidic stomach juices, or food
and fluids back up from the stomach into
the esophagus
• GERD affects people of all ages—from
infants to older adults
• The lower esophageal sphincter becomes
weak or relaxes due to,
o increased pressure on abdomen from

being overweight or obese or pregnant


o certain medicines (anti-asthmatic, calcium

channel blockers, antihistamines,


antidepressants etc.)
o smoking, or inhaling secondhand smoke

o A hiatal hernia can also cause GERD


• Proton pump inhibitors (PPIs) - lower the
amount of acid, the stomach makes
• PPIs are better at treating GERD symptoms
than H2 blockers
• They can heal the esophageal lining in most
people with GERD
•Esomeprazole
•Lansoprazole
•Omeprazole
•Pantaprazole
•Rabeprazole
(3) Lactase Deficiency
(Lactose intolerance)
• Ability to digest lactose is impaired

• 4 main causes of lactase deficiency.;


1. Primary lactose intolerance
2. Secondary lactose intolerance
3. Congenital lactose intolerance
4. Developmental lactose intolerance
Primary lactose intolerance
• A hereditary cause of lactase deficiency
• Most common type
• Gradual decrease in lactase activity since
infancy
• Symptoms in adolescence or early adulthood
• 75- 90% of adults of Asian and African origin
are lactase deficient (70- 75% of world wide)
Secondary lactose intolerance
• Injury to intestinal mucosa can cause
secondary lactase deficiency

• Common causes include:


o Gastroenteritis

o Celiac disease

o Crohn disease

o Ulcerative colitis

o Chemotherapy

o Antibiotics
Congenital Lactase Deficiency

• Rare
• Autosomal recessive inheritance
• Decrease or absence of lactase enzyme
activity since birth
• It manifests in the newborn after ingestion
of milk
Developmental Lactase Deficiency
• In premature infants born at 28 - 37 wk of
gestation – Due to the underdeveloped
intestine

• Inability to hydrolyse lactose

• This condition improves with the maturation


of intestine, which results in adequate
lactase activity
Treatment
• Reduce consumption of milk
/lactose free formula

• Intake of fermented milk


products (curd/ yoghurt)

• Calcium rich foods (non-dairy)

• Lactase treated products or


lactase containing pills
(4) Biliary deficiency
• Due to
− Impaired re-absorption from the ileum
− Biliary tract obstruction
− Severe hepatic dysfunction

• Causes poor digestion and absorption of fats


and fat-soluble vitamins

• Results in steatorrhoea - Presence of fats in


faeces cause it to be fatty, frothy, foul
smelling and floating
(5) Pancreatic exocrine insufficiency
• Synthesis and secretion of pancreatic
enzymes could be impaired in,
− Chronic pancreatitis
− Cystic fibrosis
− Surgical removal of pancreas
− Pancreatic duct obstruction

• Digestion and absorption of fats and proteins


is incomplete

• Undigested fats & proteins pass with feces


• serum enzyme tests (lipase, amylase,
trypsin)
• stool chymotrypsin
• isotopic tests based upon the assimilation of
[14C] lipids and starch or excretion of the
isotope as breath CO2
• dual-labelled Schilling test etc.
(6) Celiac disease
• Also known as celiac sprue or gluten
enteropathy

• Individuals are allergic to Gluten and closely


related proteins (in wheat, rye, barley, oats)

• This protein cause intestinal T cells to produce


an inflammatory allergic response and edema of
intestinal mucosa

• This produces malabsorption syndrome


(7) Inflammatory bowel diseases (IBD)
• Two major forms:
− Crohn's disease (CD)- any part of the GIT
− Ulcerative colitis (UC)-only in the colon
• Etiology: Genetic susceptibility +
environment + intestinal microbiota + host
immune response
• Inflammatory bowel disease (IBD) - when
the mucosal immune system exerts an
inappropriate response to luminal antigens
(such as bacteria, which may enter the
mucosa via a leaky epithelium)
(8) Irritable bowel syndrome (IBS)
• Common condition
• Symptoms: stomach cramps, bloating,
diarrhoea and constipation
• Tend to come and go over time, and can last
for days, weeks or months at a time
• Usually a lifelong problem (sometimes causes
a big impact on everyday life)
• No cure, but diet changes and medicines can
often help to control the symptoms
• Exact cause is unknown (food passing through
gut too quickly or too slowly, oversensitive
nerves in gut, stress and a family history of IBS)
Relieving IBS:
• use homemade meals
• keep a food diary - avoid things that trigger IBS
• Relax
• Exercise
• Probiotics for a month ??
• Do not delay or skip meals
• Do not eat too quickly
• Avoid fatty, spicy or processed foods
• Restrict fresh fruits (not more than 3
portions/ day - portion is 80g)
• Restrict tea or coffee
• Avoid alcohol or fizzy drinks
Oral Rehydration solution (ORS)
• In the late 1970s, acute
diarrhoea was killing around 5
million children each year
• Due to dehydration
• water - did not work because
the liquid rushed through the
digestive tract too quickly
• The only answer - intravenous
drip (invasive procedure) -
Impractical in pandemics

• One of the first large-scale field applications of


oral rehydration salts took place in 1971 during
the Bangladesh war
• When outbreaks of cholera swept through
refugee camps
• Of the 3,700 victims treated with ORS, over
96 percent survived
• About 50 million people owe their lives to
ORS solution
• ‘Potentially the most important medical
advance of the 20th century’ (British
medical journal The Lancet)
Composition
Pharmacokinetics and therapeutic
values of the substances

Glucose: facilitates the absorption of sodium


(and hence water) on a 1:1 molar basis in the
small intestine

Sodium and potassium: to replace the body


losses of these essential ions during diarrhoea
(and vomiting)

Citrate: corrects the acidosis that occurs as a


result of diarrhoea and dehydration
Advantages
• Cheap, simple and effective
• Contains the main elements lost from
diarrhea
• Should be given after every watery stool
Administrate when NO or SOME
dehydration
Home made ORS and home remedies

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