Endocrine & Metabolic

Disorders
Unit-II
Pathophysiology-II

By
Murad Ali
RN, GBSN, PGD Clinical Psychology, MSN Scholar
Objectives
By the end of this unit the students will be able to:
• Review the hypothalamic pituitary control mechanism of
hormone secretions in the body
• Discuss the functions of growth hormone
• Discuss the disorders of Growth hormone (Gigantism,
Acromegaly & Dwarfism)
 Hypothalamic Pituitary Control

• Both lobes of pituitary gland are controlled by

hypothalamus.
• Anterior lobe is regulated by releasing and inhibiting
hormones from the hypothalamus.
• The posterior lobe of the pituitary is controlled by
neuroendocrine reflexes—(the release of hormones in
response to signals from the nervous system). For example,
the suckling of an infant stimulates nerve endings in the
nipple. Sensory signals are transmitted through the spinal
cord and brainstem to the hypothalamus and from there to
the posterior pituitary. This causes the release of oxytocin,
which results in milk ejection.
 Hypothalamic Pituitary Control Cont...

• Antidiuretic hormone (ADH) is also controlled by a

neuroendocrine reflex.
• Dehydration raises the osmolarity of the blood, which is
detected by hypothalamic neurons called osmoreceptors.
• The osmoreceptors trigger ADH release, and ADH
promotes water conservation.
• Excessive blood pressure, by contrast, stimulates stretch
receptors in the heart and certain arteries.
• By another neuroendocrine reflex, this inhibits ADH
release, increases urine output, and brings blood
volume and pressure back to normal.
 Growth Hormone

• Growth hormone is regulated by two hypothalamic hormones as

GHRH and somatostatin.
• Growth Hormone (GH), or Somatotropin is secreted by
somatotropes, the most numerous cells in the anterior pituitary. The
pituitary produces at least a thousand times as much GH as any other
hormone.
• The general effect of GH is to promote mitosis and cellular
differentiation and thus to promote widespread tissue growth.
 GH cont...

• GH has widespread effect on cartilage, bone, muscle,

and fat. It exerts these effects both directly and
indirectly.
• GH itself directly stimulates these tissues, but it also
induces the liver and other tissues to produce growth
stimulants called insulin-like growth factors (IGF-I and
II), or somatomedins, which then stimulate target cells
in diverse tissues.
• Most of these effects are caused by IGF-I, but IGF-II is
important in fetal growth.
 Functions of Growth Hormone

 Protein synthesis...... Translation, transcription

• GH enhances amino acid transport into cells, and to
ensure that protein synthesis outpaces breakdown, it
suppresses protein catabolism.
 Lipid metabolism.
• To provide energy for growing tissues, GH stimulates
adipocytes to catabolize fat and release free fatty acids
(FFAs) and glycerol into the blood.
 GH Functions cont....
• GH has a protein-sparing effect—by liberating FFAs and
glycerol for energy, it makes it unnecessary for cells to
consume their proteins in growth.
 Carbohydrate metabolism.
• GH also has a glucose sparing effect. Its role in mobilizing
FFAs reduces the body’s dependence on glucose, which is
used instead for glycogen synthesis and storage.
 Electrolyte balance.
• GH promotes Na, K, and Cl retention by the kidneys,
enhances Ca2+ absorption by the small intestine, and
makes these electrolytes available to the growing tissues.
 Abnormalities in GH Secretion

 Hypersecretion of GH
• Gigantism
• Acromegaly

 Hyposecretion of GH
• Dwarfism
 Gigantism
• Gigantism is an excessive secretion of growth hormone
during childhood before the closure of the bone growth
plates, which causes overgrowth of the long bones and
very tall stature.
• Usually resulting from a tumor of somatotropes.

Robert Wadlow at age thirteen, standing 7 feet, 4 inches tall.

He suffered from Hyper Pituitarism.
 Acromegaly

• Acromegaly results when GH excess occur in adulthood or after the

epiphyseal growth of long bones stops.

• Disorder has insidious onset.

• The mean age at the time of diagnosis is about 40 for men and 45 for
women.
Clinical Manifestation
Features that result from high level of GH or expanding
tumor include:
• Soft tissue swelling of the hands and feet
• Lower jaw protrusion
• Broad and bulbous nose
• Enlarged hands
• Enlarged feet
• Arthritis and carpal tunnel syndrome
• Teeth spacing increase
• Macroglossia (enlarged tongue)
• Cardiomegaly and heart failur
• Kidney failure
Causes of Short Stature
• Variants of normal
- Genetic short stature
- Constitutional short stature
• Chronic illness and malnutrition
- Renal failure
- Nutritional deprivation
- Malabsorption syndrome
• Chromosomal disorders
- Turner’s syndrome
• Skeletal abnormalities
 Causes of Short Stature cont...

• Intrauterine Growth Retardation

• Endocrine Disorders
• GH Deficiency
• Primary......Idiopathic, Pituitary agenesis
• Secondary......panhypopituitarism
• Biologically inactive GH
• Deficient IGF-1 (Laron-type dwarfism)
• Hereditary defect in IGF receptor
• Hypothyroidism
• DM (poorly controlled)
• Glucocorticoids Excess.....exogenous, endogenous
 Pathology of Hyporsecretion of GH
 

• Pituitary tumor (nonfunctional)

• Vascular thrombosis: leads to necrosis of the normal
pituitary gland. 
• Infiltrative granulomatous disease that destroy the
pituitary.
• Idiopathic or possible autoimmune destruction of
pituitary cells.
 
 

Imran Yousafzai
B Diabetes Mellitus
Pathophysiology
Unit-II
 Objectives

• Review Anatomy & Physiology of endocrine pancreas.

• Briefly discuss the classification of diabetes mellitus
• Discuss etiology, pathophysiology, and clinical
manifestations of Type 1 DM & Type 2 DM.
• Differentiate Type 1 from Type 2 DM.
• Identify pathogenesis and manifestations of the acute and
chronic complications of diabetes mellitus.
Diabetes Mellitus
• Diabetes Mellitus is a metabolic disorder characterized by high levels
of sugar (glucose) in the blood and chronic polyuria.
• The disease was given its name because of the glucose excretion in
urine.
Classification of Diabetes Mellitus
• The disease can be classified into several types, depending on
its cause and course.
• Five forms of Diabetes Mellitus
1. Diabetes mellitus Type I
2. Diabetes mellitus Type II
3. Gestational diabetes
4. Renal diabetes
5. Diabetes insipidus
Cause
• Diabetes mellitus is caused by an absolute or relative lack of insulin
that, among other consequences, leads to an increase in plasma
glucose concentration.
IDDM or Type-I DM
• In type I (insulin-dependent diabetes mellitus [IDDM], previously
called juvenile diabetes; is characterized by the destruction of
pancreatic beta cells
Pathophysiology of DM
• The pancreatic islets are infiltrated by T-lymphocytes and
autoantibodies against islet tissue (islet cell antibodies
[ICA]) and insulin (insulin autoantibodies [IAA]) can be
detected.
 Type-II DM or NIDDM

• Type II (non-insulin-dependent diabetes mellitus

[NIDDM], formerly called maturity onset diabetes; is the
most common form of diabetes. Genetic disposition is
important. However, there is a relative insulin deficiency:
the patients are not necessarily dependent on an
exogenous supply of insulin. Insulin release can be
normal or even increased, but the target organs have a
diminished sensitivity to insulin.
Type-II DM or NIDDM

• Most of the patients with type II diabetes are

overweight.
• The obesity is the result of a genetic disposition, too
large an intake of food, and too little physical activity.
• The imbalance between energy supply and expenditure
increases the concentration of fatty acids in the blood.
• This in turn reduces glucose utilization in muscle and
fatty tissues.
• The result is a resistance to insulin, forcing an increase
of insulin release.
 Cont…

• The resulting down-regulation of the receptors further raises insulin

resistance.
• Obesity is an important trigger, but not the sole cause of type II
diabetes.
• Relative insulin deficiency can also be caused by autoantibodies
against receptors.
S&S

• In acute insulin deficiency the absence of its effect on

glucose metabolism results in hyperglycemia.
• The extracellular accumulation of glucose leads to
hyperosmolarity.
• The transport maximum of glucose is exceeded in the
kidney so that glucose is excreted in the urine.
• This results in an osmotic diuresis with renal loss of
water (polyuria), Na+, and K+, dehydration, and thirst.
Other Symptoms
• Muscular weakness.
• Hyperlipidemia.
• Kussmaul breathing.
• weight loss.
• In its most severe forms, ketoacidosis or a non–ketotic hyperosmolar
state may develop and lead to coma and, in absence of effective
treatment, death.
Management of DM
• The major components of the treatment of diabetes
are:

A • Diet and Exercise

• Oral hypoglycaemic
B therapy

C • Insulin Therapy
 Acute Complications of DM

• Diabetic ketoacidosis
• Hyperglycemia hyperosmolar state
• Hypoglycemia
• Diabetic coma
Chronic complications
• Diabetic cardiomyopathy, damage to the heart, leading
to diastolic dysfunction and eventually heart failure.
• Diabetic nephropathy, damage to the kidney which can
lead to chronic renal failure, eventually
requiring dialysis..
• Diabetic neuropathy, abnormal and decreased
sensation, usually in a 'glove and stocking' distribution
starting with the feet but potentially in other nerves,
later often fingers and hands. When combined with
damaged blood vessels this can lead to diabetic foot.
 Chronic complications cont…

• Diabetic retinopathy
• poor-quality new blood vessels in the retina as well as macular
edema (swelling of the macula), which can lead to severe vision loss or
blindness.
• Macrovascular disease leads to cardiovascular disease, to which
accelerated atherosclerosis is a contributor
• Coronary artery disease
• Leading to angina or myocardial infarction ("heart attack")
• Diabetic myonecrosis ('muscle wasting')
• Stroke (mainly the ischemic type)
 HbA1c

• Hemoglobin is the substance inside red blood cells that carries oxygen
to the cells of the body. Glucose (a type of sugar) molecules in the
blood normally become stuck to hemoglobin molecules - this means
the hemoglobin has become glycosylated (also referred to as
hemoglobin A1c, or HbA1c).
• The HbA1c test, also known as the haemoglobin A1c or glycated
haemoglobin test, is an important blood test that gives a good
indication of how well your diabetes is being controlled.
• For people without diabetes, the normal range for the hemoglobin
A1c level is between 4% and 5.6%. Hemoglobin A1c levels between
5.7% and 6.4% mean you have a higher change of getting of diabetes.
Levels of 6.5% or higher mean you have diabetes.
• For people without diabetes, the normal range for the hemoglobin
A1c level is between 4% and 5.6%. Hemoglobin A1c levels between
5.7% and 6.4% mean you have a higher change of getting of diabetes.
Levels of 6.5% or higher mean you have diabetes.
38