Index

• Megaloblastic anemia
• Hemophillia
• Iron deficiency
• Sickle cell anemia
• Parkinson’s
• schizophrenia
• Alzheimer
• Thalasemia
• Rheumatoid arthritis
• Gout diseases
• Osteoporosis
• Cancer
• Infammatory bowel disease
• Thyroid disease
Megaloblastic anemia
 What is Megaloblastic Anaemia ?

Megaloblastic anaemia is a type of anaemia

characterized by the formation of unusually
large, abnormal and immature red blood cells
called as megaloblasts by the bone marrow,
which are released into the blood.
Causes / Etiology of
Megaloblastic Anaemia

• Drugs
• Alcohol abuse
• Genetic
Symptoms of Megaloblastic Anaemia
• shortness of breath
• muscle weakness
• abnormal paleness of the skin
• glossitis (swollen tongue)
• loss of appetite/weight loss
• Diarrhea
• nausea
• fast heartbeat
• smooth or tender tongue
• tingling in hands and feet
• numbness in extremities
 Pathophysiology

Decrease in vit-B12 and Folic acid

Decreased DNA synthesis

Decreased replications and maturation

No cell division

As a result megaloblast
HOW VIT-B12 and Folic acid involved in KNA
synthesis
Diagnosis of Megaloblastic Anaemia

The doctor asks to CBC done. If anemia is

indicated in it, the peripheral smear test is
done.

Treatment
• Supplements of vit-B12 and folic acid
• Dietary intake
• Drug treatment
Iron deficiency anemia
Iron Deficiency Anemia
• "anemia" usually refers to a condition in which your
blood has a lower than normal number of red blood
cells.

• Iron is an essential mineral that is needed to form

hemoglobin, an oxygen carrying protein inside red blood
cells.

• Iron deficiency anemia is a condition in which the

body lack enough red blood corpuscles due to shortage
of iron in the body.
Pathogenesis of Iron deficiency anemia
Due to iron deficiency in the body

Abnormal RBCs start forming

Because iron is required to pro erythroblaste to convert into

mature RBCs .
 Etiology / Causes

• Blood loss = during menstrual period

• Decreased acidity in stomach or eaten antacids
in high amount.
Treatment
• Dietary intake = meat, egg, Banana, spinach,
• Blood transfusion.
• Iron suppliment
 Sickle cell anaemia
Sickle cell anaemia is a serious disease in which the body
makes sickle-shaped ("c"-shaped) red blood cells.

Normal red blood cells are disk-shaped and move easily

through your blood vessels.

Sickle cells contain abnormal haemoglobin that causes

the cells to have a sickle shape, which don’t move easily
through the blood vessels – they are stiff and sticky and
tend to form clumps and get stuck in the blood vessels.

Blocked blood vessels can cause pain, serious infections,

and organ damage.
 Characteristics of sickle cells
Red blood corpuscles Sickle cell anemia
• 120 day life span • 30-40 day life span

• Hb has normal oxygen • Hb has decreased oxygen

carrying capacity carrying capacity

• 12-14 g/dl of Hb • 6-9 g/dl of Hb

 Sign & symptoms
• excessive fatigue or irritability, from
anemia
• bedwetting, from associated kidney
problems
• jaundice, which is yellowing of the eyes
and skin
• swelling and pain in hands and feet
• frequent infections
• pain in the chest, back, arms, or legs
 Pathogenesis
Sickle-cell anaemia is caused by point mutation

in β-globin chain of haemoglobin having the amino acid

glutamic acid

to be replaced with the hydrophobic amino acid valine at

the sixth position

β-globin gene is found on the short arm of chromosome 11

association of two wild-type α-globin subunits with two

mutant β-globin subunits forms haemoglobin S (HbS)
 Under low-oxygen conditions (oxygenation
Pathophysiology

the absence of a polar amino acid at position six of

the β-globin chain

promotes the non-covalent polymerisation of

haemoglobin (aggregation)

which distorts red blood cells into a sickle shape and

decreases their elasticity

Sickle shaped RBCs blocks blood vessel

Blocked blood vessels can cause pain, serious

infections, and organ damage.
 Diagnosis
• Sickle solubility tests look for the presence of Hb S.
• CBC test can reveal an abnormal Hb level.
• Peripheral smear
• CT scan & MRI
• Hemoglobin electrophoresis
Of Beta Thalassemia
Sign and symptoms
• Fatigue.
• Weakness.
• Pale or yellowish skin.
• Facial bone deformities.
• Slow growth.
• Abdominal swelling.
• Dark urine.
• Perform splenectomy if blood transfusion requirement
increased.
Hemophilia
Intrinsic pathways factor of
blood clotting
Rheumatoid arthritis
 Definition / Introduction
• Rheumatoid arthritis (RA) is an autoimmune disease that
results in a chronic, systemic inflammatory disorder that may
affect many tissues and organs, but principally attacks
synovial joints.
• Rheumatoid arthritis is characterized by synovial
inflammation and hyperplasia (“swelling”),autoantibody
production (rheumatoid factor and anti–citrullinated protein
antibody[ACPA]), cartilage and bone destruction
(“deformity”), morning stiffness and systemic features,
including cardiovascular, pulmonary, psychological, and
skeletal disorders.
• The disorder is much more common in women than in men.

• Genetic and autoimmune factors are mainly responsible for

the initiation of disease process.
Etiology
• The cause of RA is unknown.
• Following reason may cause RA

1. Immunologic factor
2. Genetic factor
3. Infectious agent
4. Hormonal factor
5. Increased serum and synovium rheumatoid
factor
6. Other factors include Smoking, Vitamin-C
deficiency
Pathophysiology

In response to any etiological factor , CD4+ T cells are activated.

These cells elaborate cytokines, the important ones being

tumour necrosis factor (TNF)-α, interferon (IF)-γ , interleukin (IL)-
1 and IL-6.

These cytokines activate endothelial cells, B lymphocytes and

macrophages.

Activation of B-cells releases IgM antibody against IgG (i.e. anti-

IgG); this molecule is termed rheumatoid factor (RF).

IgG and IgM immune complexes trigger inflammatory damage to

the synovium(synovial membrane) , small blood vessels and
collagen.
Activated endothelial cells express adhesion molecules which
stimulate collection of inflammatory cells.

Activation of macrophages releases more cytokines &

proteases which cause damage to joint tissues and
vascularisation of cartilage termed pannus formation.

Eventually damage and destruction of bone and cartilage are

followed by fibrosis and ankylosis producing joint deformities
Sign and Symptoms
• Pain
• Swelling
• Stiffness
• Redness and warmth
• Inflammation

Other
• Fatigue
• Loss of appetite, which can lead
to weight loss,
• Muscle aches.
Diagnosis
• Rheumatoid factor test
• Anti cyclic citullinated peptide antibody test
• WBC count
• Erythrocyte sedimentation Rate

Treatment

NSAIDs: NSAIDs may reduce inflammation and relieve pain. NSAIDs

include Ibuprofen, Indomethacin, Diclofenac sodium, Aceclofenac
and Naproxen.

Acetaminophen: Acetaminophen can relieve pain, but it does not

reduce inflammation.

Immunosuppressive therapy
surgery
• Rheumatoid factors are present Rheumatoid factors are absent
Gout diseases
 Introduction
Gout is a common arthritis caused by deposition of monosodium urate crystals within joints
after chronic hyperuricaemia.

Hyperuricaemia is caused due to increased production of urea & decreased excretion of urea.

It affects 1–2% of adults in developed countries.

Gout and hyperuricaemia are associated with hypertension, diabetes mellitus, metabolic
syndrome, and renal and cardiovascular diseases.

Non-steroidal anti-inflammatory drugs and colchicine remain the most widely recommended
drugs to treat acute attacks.

Interleukin 1β is a pivotal mediator of acute gout and could become a therapeutic target.

The prevalence of gout is much higher in men than in women and rises with age. In women it
mainly develops after menopause—the fall in oestrogen, which is uricosuric, increases
uricaemia.

Uricosurics are drugs that promote the excretion of uric acid and are used in patients who have
gout
Etiology
• Age and gender:
• Genetics:
• Lifestyle Factors: obesity, alcohol consumption
• Lead exposure
• Medications: Certain medications can increase the levels of uric acid in
the body, such as diuretics and drugs containing salicylate, Niacin etc.
• Other health problems : hypertension, diabetes mellitus, metabolic
syndrome, and renal and cardiovascular diseases.
• The prevalence of gout in men increases with high consumption of meat,
seafood, and fructose, and intake of beer and spirits,
• vegetables with a high purine content.
Pathophysiology

Uric acid is the final metabolite of endogenous and dietary purine

metabolism

Due to increased production of uric acid and decreased excretion of

uric acid result into hyperuricaemia.

Due to Chronic hyperuricaemia monosodium urate ( MSU ) crystals

deposited in the soft tissue & joints

MSU activates cytokines that recruit macrophages .

Macrophages phagocytose the MSU ( monosodium urate ) and the

intracellular sensor, the inflammasome , recognizes the crystals. The
inflammasome activates caspase-1, which is involved in the production
of some biologically active cytokines, most notably IL-1.
IL-1 is proinflammatory, and promotes accumulation of
neutrophils and macrophages in the joint. These cells, in turn,
release other cytokines, free radicals, proteases and
arachidonic acid metabolites ( postaglandins ) , all of which
recruit more leukocytes and damage the joint.

Urate crystals may also activate the complement system,

leading to the generation of chemotactic complement
byproducts. These cascades trigger an acute arthritis,

In tissues, formation of monosodium urate crystals depends on

several factors—particularly on
• local concentration of urate.
• Solubility of urate in joint fluids depends on the articular
hydration state,
• temperature,
• pH,
• concentration of cations,
• and presence of extracellular matrix proteins such as proteoglycans,
collagens, and chondroitin sulphate.
• Heavy alcohol consumption
• Obesity
• Drugs (e.g., thiazides) that reduce excretion of urate
• Lead toxicity
• Genetics
Sign & symptoms
• sever pain,
• bone erosion,
• redness and swelling in joints,
• often the big toe.

Rare symptoms
Fatigue
High fever
Leukocytosis

Complications
People with gout can develop more severe conditions, such as:
• Recurrent gout
• Kidney stones
Diagnosis
• Joint fluid test: Joint fluid test (arthrocentesis) is useful to see whether uric acid
crystals are present. This is the only test for diagnosis of gout
• Urine test: A test to measure levels of uric acid in urine.
• Blood test: To measure the uric acid level in blood.
• X-rays

Treatment
NSAIDs: NSAIDs may control inflammation and pain in people with gout. NSAIDs
include indomethacin, ibuprofen, naproxen, and etoricoxib.

Colchicine: A type of pain reliever that effectively reduces gout pain, especially when
started soon after symptoms appears.

Corticosteroids: Corticosteroid medications, such as the drug prednisone, may

control gout inflammation and pain Corticosteroids are generally reserved for people
who cannot take either NSAIDs or colchicine.
• Medications that block uric acid production: Allopurinol drug & febuxostat
inhibits Xanthene oxidase enzymes.

• Medication that improves uric acid removal: Probenecid improves kidney’s

ability to remove uric acid from body.

• Pegloticase: This medicine is for gout that has lasted a long time and has
not responded to other treatment.
Osteoporosis
The term osteopenia refers to decreased bone mass,

and osteoporosis is defined as osteopenia that is

severe enough to significantly increase the risk of
fracture.
Cancer
Neoplastic Cell / Cancer cell Characteristics
• Uncontrolled proliferation
• Dedifferentiation and loss of function
• Invasiveness
• Metastasis.

Uncontrolled proliferation: Normal cell division and tissue growth occurs by

regulatory processes but proliferation of cancer cell is not controlled by these
processes and leads to uncontrolled proliferation which varies from type to
type.

Dedifferentiation & loss of function: unlike normal cell, cancer cell do

uncontrolled differentiation and they loss their normal functions.

Invasiveness: due to uncontrolled proliferation and differentiation tumor is

formed which spread to healthy cell .

Metastasis: primary tumor migrate to another site and form secondary

tomor.
 Difference between benign &
malignant tumor.
Benign Malignant
• It is a non-cancerous • It is a cancerous tissue
tissue. • It shows metastasis and
• Benign tumor does not thus invades other body
show metastasis and is parts
non invasive • Malignant tumor shows
• It stops growth after indefinite growth
reaching a certain size • There is no adherence
• Limited adherence occurs amongst cell. They tend
amongst cells of benign to slip past one another.
tumor • It is more fatal to the
• It is less fetal to the body. body.
Cancer is a diseases which is caused due to uncontrolled cell proliferation and
differentiation.

CLASSIFICATION OF CANCER

1. Classification by Site of Origin

By primary site of origin, cancers may be of specific types like
• Breast cancer
• Lung cancer
• Prostate cancer
• Liver cancer
• Renal cell carcinoma (kidney cancer),
• Oral cancer
• Brain cancer etc.
Classification by Tissue Types
1. Carcinoma: This type of cancer originates from the epithelial layer of cells of
ectoderm and endoderm that form the lining of external parts of the body or the
internal linings of organs within the body.

It accounts for 85% of all cancers.

It is mainly occur in Breast, liver, kidneys, prostate, ovaries, thyroid, colon, stomach,
salivary gland, lungs etc.

2. Sarcoma: These cancers originate in connective and supportive tissues including

muscles, bones, cartilage and fat.

It affects the young most commonly.

2% of all cancer

Bone, cartilage, fatty tissue, vessels etc.

4. Leukemia: This group of cancers are grouped within blood cancers. These cancers
affect the bone marrow which is the site for blood cell production.

When cancerous, the bone marrow begins to produce excessive immature white blood
cells that fail to perform their usual actions and the patient is often prone to infection.

4% of all cancers

5. Lymphoma: These are cancers of lymphatic system. It mainly affects the lymph nodes.
In which there is excessive production of lymphocytes by lymph nodes and spleen
nodes.

Lymphomas may be of two types –

Hodgkin’s lymphoma and Non-Hodgkin’s lymphomas.

In Hodgkin lymphoma there is characteristic presence of Reed-Sternberg cells in the

tissue samples which are not present in Non-Hodgkin lymphoma.
Etiology

Environmental and life style factor: Environmental and life style factors include
geographic location, cigarette smoking
Pathogenesis
In response to any etiological factor , DNA of normal cell get
damaged as a result mutation in the genome of somatic cell take
place Which may leads to activation of proto-oncogenes to
oncogenes and inactivation of tumor suppressor genes as well as
alteration in gene that regulates apoptosis which may lead to
uncontrolled proliferation and differentiation of cell as result
primary tumor is formed. primary tumor in presence of
metalloproteinase shows metastasis and form secondary tumor.
Schizophrenia
Schizophrenia
Schizophrenia is a chronic and sever mental disorder that is a important form of psychiatric
illness affects how a person think, feels, and behave.

Schizophrenia patients are Fail to differentiate between reality and false beliefs
characterized by hallucination, delusions and other cognitive difficulties,

Hallucination : A perception of having seen, heard, touched, tasted or smelled something

that wasn’t actually there.

Delusion: A false belief

Symptom:
The symptom of schizophrenia falls into three categories: positive , negative and Cognitive.

Positive symptoms
It includes the following symptoms:
1. Hallucination
2. Delusion
3. Movement disorder
4. Thought disorder
Negative symptoms
It includes the following symptoms.
1. Reduced expression of emotion via facial expression or voice.
2. Reduced felling of pleasure
3. Withdrawn from social contact

Cognitive symptoms
In which cognitive function of patient reduces like attentiveness , learn, memory loss.
The Dopamine Hypothesis
The dopamine hypothesis of schizophrenia postulates that
hayperctivity of dopamine D2 receptor neurotransmission in
subcortical and limbic brain regions contributes to positive
symptoms of schizophrenia, whereas negative and cognitive
symptoms of the disorder can be attributed to hypofunctionality
of dopamine D1 receptor neurotransmission in the prefrontal
cortex.

In support of this, studies have shown an increased density of

the dopamine D2 receptor in postmortem brain tissue of
schizophrenia sufferers (Seeman et al., 2000). It is also reported
that upregulation of D2 receptors in the caudate nucleus of
patients with schizophrenia directly correlates with poorer
performance in cognitive tasks involving corticostriatal pathways
• Decreased glutaminergic pathway contributes to schizophrenia.
• NMDA is a glutamate receptor.
Treatment
Schizophrenia requires lifelong treatment, even when symptoms have subsided

Medications: following are the medicines that are prescribed by doctor when patient is
suffering from schizophrenia.
• Aripiprazole (Abilify) • Asenapine (Saphris) • Brexpiprazole (Rexulti) • Cariprazine
(Vraylar) • Clozapine (Clozaril) • Iloperidone (Fanapt)

Psychosocial interventions: Psychosocial interventions includes

• Individual therapy: Psychotherapy may help to normalize thought patterns. Also,
learning to cope with stress and identify early warning signs of relapse can help people
with schizophrenia manage their illness.
• Social skills training: This focuses on improving communication and social interactions
and improving the ability to participate in daily activities.
• Family therapy: This provides support and education to families dealing with
schizophrenia.

Electroconvulsive therapy (ECT): This is a procedure in which a series of electric shocks

are delivered to the brain. The shocks induce seizures, causing the release of
neurotransmitters in the brain. This form of treatment is rarely used today in the
treatment of schizophrenia. ECT may be useful when all medications fail or if severe
depression or catatonia makes treating the illness difficult.
ECT: Electroconvulsive therapy
 Alzheimer Disease
• Alzheimer disease (AD) is the most common cause of
dementia in older adults, with an increasing incidence ( rate
of something )as a function of age.
• The fundamental abnormality in AD is the accumulation of
two proteins (Aβ and tau) in specific brain regions, likely as a
result of excessive production and defective removal
The amyloid or senile plaques (SPs) are constituted chiefly of highly insoluble
and proteolysis-resistant peptide fibrils produced by β-amyloid (Aβ) cleavage.
The Stages of Alzheimer’s Disease
pre-clinical or the pre-symptomatic stage, which can last for several years or more. This stage
is characterized by mild memory loss and early pathological changes in cortex and
hippocampus, with no functional impairment in the daily activities and absence of clinical
signs and symptoms of AD.

The mild or early stage of AD, where several symptoms start to appear in patients, such as a
trouble in the daily life of the patient with a loss of concentration and memory, disorientation
of place and time, a change in the mood, and a development of depression.

Moderate AD stage, in which the disease spreads to cerebral cortex areas that results in an
increased memory loss with trouble recognizing family and friends, a loss of impulse control,
and difficulty in reading, writing, and speaking.

Severe AD or late-stage, which involves the spread of the disease to the entire cortex area
with a severe accumulation of neuritic plaques and neurofibrillary tangles, resulting in a
progressive functional and cognitive impairment where the patients cannot recognize their
family at all and may become bedridden with difficulties in swallowing and urination, and
eventually leading to the patient’s death due to these complications.
Alzheimer’s Disease Hypotheses
1. Cholinergic Hypothesis: Due to the essential role of ACh in cognitive function, a
cholinergic hypothesis of AD was proposed.

In the brain, ACh is involved in several physiological processes such as memory,

attention, sensory information, learning, and other critical functions. Degeneration
of the cholinergic neurons was found to take place in AD and to cause alternation in
cognitive function and memory loss. B-amyloid is believed to affect cholinergic
neurotransmission and to cause a reduction in the choline uptake and a release of
ACh.

2. Amyloid Hypothesis: The amyloid hypothesis suggests that the degradation of Aβ,
derived from APP by β- and γ-secretase, is decreased by age or pathological
conditions, which leads to the accumulation of Aβ peptides (Aβ40 and Aβ42).
Increasing the ratio of Aβ42/Aβ40 induces Aβ amyloid fibril formation, resulting in
neurotoxicity and tau pathology induction, and consequently, leading to neuronal
cell death and neurodegeneration.
 Pathogenesis of Alzheimer diseases

Due to some etiological factor, changes occur in the amyloid

precursor protein and tau which result into the intraneuronal
accumulation of neurofibrillary tangle and extracellular deposition of
beta amyloid plaques and loss of cortical cholinergic neurons
happens which may lead to neurotoxicity and consequently, leading
to neuronal cell death and neurodegeneration as result memory
impairment and , loss of cognition and judgment ,attentiveness
occurs.
Parkinson’s diseases
Parkinson’s diseases
PD is a progressive disorder of movement that is characterized by
• suppression of voluntary movements (bradykinesia),
• tremor at rest
• muscle rigidity, detectable as an increased resistance in passive limb movement;
• a variable degree of cognitive impairment

PD is degeneration of neurones in the substantia nigra pars compacta (SN-PC) and the
nigrostriatal (dopaminergic) tract. This results in deficiency of dopamine (DA) in the striatum
which controls muscle tone and coordinates movements. An imbalance between
dopaminergic (inhibitory) and cholinergic (excitatory) system in the striatum occurs giving
rise to the motor defect.
Symptoms

Tremors:
Slowed movement (Bradykinesia):
Rigid muscle:
Impaired posture and balance:
Loss of automatic movements:
Speech changes
Writing changes:
Pathophysiology of Parkinson’s diseases
the basal ganglia provides modulatory input to the motor cortex. The striatal GABAergic
neurones receive side-loop excitatory glutamatergic (Glu) input from the motor cortex
and modulatory dopaminergic (DA) projections from the substantia nigra pars compacta
(SN-PC). There are also balancing cholinergic (ACh) interneurones. The striatal neurones
express both excitatory D1 and inhibitory D2 receptors. The output from the striatum to
substantia nigra pars reticulata (SN-PR) and internal globus pallidus (GP-I) follows a
direct and an indirect pathway. The direct pathway modulated by DI receptors releases
inhibitory transmitter GABA and inhibit the SNPR and GP1 to release GABA
neurotransmitter, so thalamus keep on releasing glutamate and stimulates motor cortex
and controls voluntary movement while the dominant indirect pathway modulated by
D2 receptors has two inhibitory (GABAergic) relays and an excitatory (glutamatergic)
terminal and excite the SNPR and GP1 through glutamate and stimulate the release of
inhibitory neurotransmitter GABA which act on thalamus and inhibits the release of
glutamate and inhibits the voluantary movement . Due to this arrangement,
dopaminergic action in the striatum exerts inhibitory and exitatory influence on SNPR
and GP-I via.

The degenerative lesion (in SN-PC) of Parkinson’s disease (PD) decreases dopaminergic
input to the striatum, producing an imbalance between DA and ACh, resulting in
hypokinesia, rigidity , broadykinasia and tremor.
Thyroid diseases
Hypothyrodism
Hypothyroidism is a condition caused by a structural or functional derangement of thyroid
gland that result into decrease in the production of thyroid hormone.
Diagnosis
A diagnosis of hyperthyroidism is made using both clinical and laboratory
findings. The measurement of serum TSH concentration is the most useful single
screening test for hyperthyroidism, because its levels are decreased even at the
earliest stages, when the disease may still be subclinical.
Biosynthesis of thyroid hormone
The thyroid gland is the only endocrine gland that stores its secretory product in large
quantities—normally about a 100-day supply. Synthesis and secretion of T3 and T4 occurs as
follows

1. Iodide trapping. Thyroid follicular cells trap iodide ions (I-) by actively transport from the
blood into the cytosol. As a result, the thyroid gland normally contains most of the
iodide in the body.
2. Synthesis of thyroglobulin. While the follicular cells are trapping I-, they are also
synthesizing thyroglobulin (TGB) ,a large glycoprotein that is produced in the rough
endoplasmic reticulum, modified in the Golgi complex, and packaged into secretory
vesicles. The vesicles then undergo exocytosis, which releases TGB into the lumen of the
follicle.
3. Oxidation of iodide. Some of the amino acids in TGB are tyrosines that will become
iodinated. However, negatively charged iodide ions cannot bind to tyrosine until they
undergo oxidation (removal of electrons) to iodine: 2 I- → I2. As the iodide ions are being
oxidized, they pass through the membrane into the lumen of the follicle.
4. Iodination of tyrosine. As iodine molecules (I2) form, they react with tyrosines
that are part of thyroglobulin molecules. Binding of one iodine atom yields
monoiodotyrosine (T1), and a second iodination produces diiodotyrosine (T2). The
TGB with attached iodine atoms, a sticky material that accumulates and is stored in
the lumen of the thyroid follicle, is termed colloid.

5. Coupling of T1 and T2. During the last step in the synthesis of thyroid hormone,
two T2 molecules join to form T4, or one T1 and one T2 join to form T3.

6. Pinocytosis and digestion of colloid. Droplets of colloid reenter follicular cells by

pinocytosis and merge with lysosomes. Digestive enzymes in the lysosomes break
down TGB, cleaving off molecules of T3 and T4.

7. Secretion of thyroid hormones. Because T3 and T4 are lipidsoluble, they diffuse

through the plasma membrane into interstitial fluid and then into the blood. T4
normally is secreted in greater quantity than T3, but T3 is several times more
potent. Moreover, after T4 enters a body cell, most of it is converted to T3 by
removal of one iodine.

8. Transport in the blood. More than 99% of both the T3 and the T4 combine with
transport proteins in the blood, mainly thyroxine-binding globulin (TBG).
Regulation of Thyroid hormones
Thyrotropin-releasing hormone (TRH) from the hypothalamus and thyroid-stimulating
hormone (TSH) from the anterior pituitary stimulate synthesis and release of thyroid
hormones, as follow

1. Low blood levels of T3 and T4 or low metabolic rate stimulates the hypothalamus to
secrete TRH.

2. TRH enters the hypophyseal portal veins and flows to the anterior pituitary, where it
stimulates thyrotrophs to secrete TSH.

3. The binding of TSH to its receptor on the thyroid follicular epithelium results in activation
of the receptor, allowing it to associate with a Gs protein . Activation of the G protein
stimulates downstream events that result in an increase in intracellular cAMP levels,
which stimulates thyroid growth and thyroid hormone synthesis and release via cAMP-
dependent protein kinases.

4. The thyroid follicular cells release T3 and T4 into the blood until the metabolic rate
returns to normal.

5. An elevated level of T3 inhibits release of TRH and TSH (negative feedback inhibition).
Actions of Thyroid Hormones
Because most body cells have receptors for thyroid hormones, T3 and T4 exert their effects
throughout the body.

1. Thyroid hormones increase basal metabolic rate (BMR), the rate of oxygen
consumption under standard or basal conditions (awake, at rest, and fasting), by
stimulating the use of cellular oxygen to produce ATP. When the basal metabolic rate
increases, cellular metabolism of carbohydrates, lipids, and proteins increases.

2. A second major effect of thyroid hormones is to stimulate synthesis of additional

sodium–potassium pumps (Na–K ATPase),

3. In the regulation of metabolism, the thyroid hormones stimulate protein synthesis and
increase the use of glucose and fatty acids for ATP production. They also increase
lipolysis and enhance cholesterol excretion, thus reducing blood cholesterol level.

4. [ The thyroid hormones enhance some actions of the catecholamines (norepinephrine

and epinephrine) because they upregulate beta () receptors. ] For this reason,
symptoms of hyperthyroidism include increased heart rate, more forceful heartbeats,
and increased blood pressure.
5. [ Together with human growth hormone and insulin, thyroid
hormones accelerate body growth, particularly the growth of the
nervous and skeletal systems. ] Deficiency of thyroid hormones during
fetal development, infancy, or childhood causes severe mental
retardation and stunted bone growth.
 Inflammatory bowel diseases
• Inflammatory bowel diseases represent a group of intestinal disorder that cause
prolonged inflammation in the gastrointestinal tract.

• It is a spectrum of chronic idiopathic inflammatory condition.

Inflammatory bowel diseases can be classified into two types

1. Ulcerative colitis: ulcerative colitiis is a diseases that causes mucosal infection and
sores in the lining of the large intestine mainly colon.

2. Crohn’s diseases: Crohn’s disease may involve any portion of the gastrointestinal tract
but affect most commonly 15-25 cm of the terminal ileum which may extend into the
caecum and sometimes into the ascending colon.

Ulcerative colitis is slightly more common in males while crohn’s disease is more frequent
in women.

Both ulcerative colitis and Crohn's disease usually involve severe diarrhoea, abdominal
pain, and fatigue and weight loss.
Sign and symptoms of IBD

Inflammatory bowel disease symptoms vary, depending on the severity of

inflammation and where it occurs. Symptoms may range from mild to severe. Signs
and symptoms that are common to both Crohn's disease and ulcerative colitis
include:

Diarrhoea,
fever and fatigue,
abdominal pain and cramping,
blood in stool,
reduced appetite,
unintended weight loss.
Etiology
The exact cause of IBD is unknown, but it may cause due to following reasons.

1. Impaired immunology: A properly functioning immune system attacks foreign

organisms, such as viruses and bacteria, to protect the body. In IBD, the immune system
responds incorrectly to environmental triggers, which causes inflammation of the
gastrointestinal tract.

2. Genetic factor: due to genetic factor, There is approximately 50% chance of

development of IBD (Crohn’s disease about 60%, ulcerative colitis about 6%) in
monozygotic twins. However there is no clear link between the abnormal genes and IBD

3. Microbial factor: Microbial factors (bacteria, viruses, protozoa and fungi) have been
suspect but without definite evidence

4. Environmental factor: it includes improper diet, smoking, etc.

5. Psychosocial factor: it includes illness or death in the family, divorce, interpersonal

conflicts etc. might suffer from IBD.