Adrenal gland
Dr T TADERERA
Anatomy
• There are 2 adrenal glands each weighing
about 4 gms
• They lie at the superior poles of the two
kidneys
• Each gland is composed of two distinct
parts adrenal cortex and adrenal medulla
• Blood supplied by superior ,inferior and
middle adrenal arteries
location
Section of adrenal gland
•Zona glomerulosa (15%) secretes
aldosterone
•Zona fasciculata (50%) secretes cortisol
•Zona reticulata (7%) secretes androgens
•In the fetus the cortex is also made up
of a fetal adrenal cortex
•It produces sulfate conjugates of
androgens which are converted to
estrogens in the placenta
•It rapidly degenerates at the time of
birth
Aldosterone & cortisol
most imp
Adrenal cortex
• Hormones are derivatives of cholesterol
• They contain a
cyclopentanoperhydrophenathrene nucleus
Three distinct layers• Zona glomerulosa- thin layer under the
capsule 15% of the cortex. The cells here are
capable of secreting significant amount of
aldosterone (mineralcorticoid)
• Zona fasiculata- middle widest layer 75%of
cortex secreting glucocorticoids (cortisol and
corticosterone)
• Zona reticularis- small amounts of adrenal
androgens
Adrenal medulla
• It occupies the central 28 % of the adrenal
gland
• It secretes the hormones epinephrine and
nor epinephrine in response to
sympathetic stimulation they are referred
to as catecholamines
MORPHOLOGY OF ADRENAL GLAND
•Medulla
•There are 2 major cell types in the
medulla
•- large, less dense granules secreting
epinephrine
•- small very dense granules secreting
norepinephrine
Biosynthesis of adrenal steroids
• Adrenocorticoids are steroids derived from cholesterol
• Important steroid products of adrenal cortex are
aldosterone , cortisol and androgens
• All the steps of synthesis occur in the mitochondria
and endoplasmic reticulum
• Approx 90-95% of cortisol in plasma binds to plasma
protein globulin called transcortin and to <albumin
• Binding serves as a reservoir to lessen rapid
fluctuations in free hormone concentration (t1/2
60-90mins)
• Only 60% of aldosterone is bound & so (t1/2 20mins)
• Adrenal steroids are degraded mainly by liver and
conjugated to glucuronic acid or < sulphates
• Liver diseases markedly depress the rate of
inactivation
Aldosterone synthase
Aldosterone
•C19 steroids – have androgenic activity
•C21 steroids – have mineralocorticoid or
glucocorticoid activity
Mineralocorticoids
• Aldosterone- very potent & accounts for
90% of all mineralocorticoid activity.
• Desoxycorticosterone (1/30 as potent as
aldosterone, small quantities secreted
• Corticosterone-slight mineralocorticoid
activity
• Cortisol- very slight mineralocorticoids
activity, but large quantities secreted
• Cortisone- synthetic, slight
mineralocorticoid activity
Glucocorticoids
• Cortisol- very potent, accounts for 95% of
all glucocorticoid activity.
• Corticosterone- provides 4% of total
glucocorticoid activity, but less potent
than cortisol
• Cortisone- synthetic, almost as potent as
cortisol
• Prednisone- synthetic, 4x as potent as
cortisol
• Dexamethasone-synthetic, 30x as potent
ADRENAL CORTEX
• ZONA GLOMERULOSAMINERALOCORTICOID- ALDOSTERONE
Mineralocorticoid- aldosterone
• Aldosterone is the principal mineralocorticoid
secreted by the adrenal glands
• Aldosterone exerts 90% of the mineralocorticoid
activity of adrenal cortex rest 10 % is by cortisol
• Aldosterone increases the reabsorption of
sodium ions in the ECF
• It acts on principal cells of collecting ducts in
the kidney increasing sodium in exchange of
potassium and hydrogen ions
Nephron
Aldosterone
• Is a mineralocorticoid
• The major stimuli affecting its secretion
is Angiotensin II although ACTH is
involved in its secretion in response to
stress
Renin Angiotensin Aldosterone
System
• The renin angiotensin aldosterone system
(RAAS) is important for long term
regulation of blood pressure
• This system is activated by a decrease in
perfusion to kidney
• The components of the RAAS include
• - renin (secreted by the kidney)
• - angiotensinogen (produced by the liver)
• - angiotensin converting enzymes (ACE)
• - aldosterone
RAAS
Decrease in perfusion
Increase in renin secretion
Angiotensinogen split to form Angiotensin I
ACE in lungs/kidneys converts
AT I to AT II
Angiotensin II has direct effects or increase
the secretion of aldosterone
AT Il activates IP3 to synthesise aldosterone
Renin
• Is produced in the kidney in response to a
decrease in perfusion
• It is secreted by the juxtaglomerular cells (JGA)
• Renin is synthesised as a preprohormone and
cleaved to form prorenin
• Prorenin has little if any biologic activity
• Prorenin is also secreted by other sources e.g.
the placenta but the kidney is virtually the only
organ which converts prorenin to renin
• Thus kidney is the primary source of renin
Renin
• Prorenin is also secreted by other sources
e.g. the placenta but the kidney is
virtually the only organ which converts
prorenin to renin
• Thus kidney is the primary source of renin
STIMULI AFFECTING RENIN SECRETION
Increasing secretion
Decreasing secretion
•Low Na content in blood
•Low blood flow in the
kidney
•B adrenergic stimulation
•low K concentration
• high Na concentration
• aldosterone
• vasopressin
Angiotensinogen
• Circulating angiotensinogen is found in
the α2 – globulin fraction of plasma
• It is synthesised by the liver and is the
precursor for AT II
• Its circulation is increased by
glucocorticoids, thyroid hormones,
estrogens, several cytokines and
angiotensin II
Angiotensin Converting Enzyme (ACE)
• Splits AT I to AT II and also inactivates bradykinin
(kininase II)
• It is located in endothelial cells of capillaries
• Much of the conversion occurs as blood passes
through the lungs
• ACE is also found in appreciable quantities in
the kidney (20% of circulating AT II produced in
the kidney)
• ACE is found in most parts of the body (?local
control of blood pressure)
Angiotensinogen
• Circulating angiotensinogen is found in
the α2 – globulin fraction of plasma
• It is synthesised by the liver and is the
precursor for AT II
• Its circulation is increased by
glucocorticoids, thyroid hormones,
estrogens, several cytokines and
angiotensin II
Angiotensin Converting Enzyme (ACE)
• Splits AT I to AT II and also inactivates bradykinin
(kininase II)
• It is located in endothelial cells of capillaries
• Much of the conversion occurs as blood passes
through the lungs
• ACE is also found in appreciable quantities in
the kidney (20% of circulating AT II produced in
the kidney)
• ACE is found in most parts of the body (?local
control of blood pressure)
Metabolism of Angiotensin II
• AT II is metabolised rapidly and its half
life is 1 – 2 mins in humans
• An aminopeptidase cleaves AT II to form
AT III and AT III is in turn converted to AT
IV by the same enzyme
• AT III retains aldosterone secreting ability
and AT IV has the same activity
• Angiotensin metabolising activity is found
in red blood cells and many tissues
Actions of Angiotensins
• Act on either ATR1 (chrom 3)
• ATR2 (X chromosome) receptors
• other receptors which have not been fully characterised
THROUGH ATR2 IT CAUSES
Vasodilatation
Natriuresis
Growth arrest and apoptosis
Cognitive function
ATR2 are more plentiful in fetal and
neonatal life (No wonder why ACE
inhibitors and AT blockers are
contraindicated in pregnancy)
• These receptors are also expressed in
adult brain and in the placenta (Exp
Physiol 2004; 90(3):277)
•
•
•
•
•
THROUGH ATR1 IT CAUSES
• Vasoconstriction
• Increase glomerular filtration rate
• Increase sodium retention by kidney
(tubular reabsorption)
• cell growth & proliferation (growth factor
to heart)
• Increase secretion of ADH & ACTH secretion
• Increase secretion of aldosterone (water
retention)
Regulation of Renin Secretion
• Intrarenal baroreceptor mechanisms that causes
renin secretion to decrease when arteriolar
pressure at level of JG cells increases
• Secretion also regulated by NaCl delivered to
distal tubule (macula densa)
• AT II feeds back to inhibit renin secretion and
vasopressin also inhibits renin
• Β adrenergic fibers increase renin secretion
• Prostagladins also increase renin secretion
• Psychologic stimuli increases renin secretion as
well
Pharmacologic Manipulation of the
RAAS
• Inhibitors of prostaglandins synthesis such
as indomethacin, B blocking drugs
(propanolol) reduces renin secretion
• ACE inhibitors such as captopril, enalapril
and ATR antagonists such as losartan
(selectively inhibits ATR1) are used in the
management of hypertension
Pharmacologic Manipulation of the
RAAS
• Aliskiren (developed in 2007), a renin
inhibitor promises to be drug for the
future
• Black hypertensives have low renin levels
STIMULI INCREASING ALDOSTERONE
SECRETION
•
•
•
•
•
•
•
•
Surgery
Anxiety
Physical trauma
High K intake
Low Na intake
Constriction of IVC in thorax, hemorrhage
Standing
Circadian rhythm
Effects of aldosterone
• Increases activity of Na pump
• Increased absorption of Na (through
increased synthesis ENa channels)
• Increased potassium and hydrogen
excretion in kidney
• Cardiac growth factor (use of
antagonists in C. Failure)
Effect of cortisol in preventing
inflammation ….
• Cortisol stabilizes the lysosomal membrane
• Cortisol decreases the permeability of the
capillaries preventing loss of plasma into tissues
• Cortisol decreases migration of WBCs into
inflamed area and phagocytosis of damaged
cells
• Cortisol suppresses the immune system causing
lymphocyte production to decrease
• Cortisol attenuates fever as it reduces the
release of interleukin-1
NB:
In endocrinology, permissiveness is a biochemical phenomenon
in which the presence of one hormone is required in order for
another hormone to exert its full effects on a target cell.
Hormones can interact in permissive, synergistic, or
antagonistic ways.
Effects of increased cortisol levels during stress
• Effects on organic metabolism
a. Stimulation of protein catabolism in bone, lymph, muscle etc.
b. Stimulation of liver uptake of amino acids and their conversion
to glucose (gluconeogenesis).
c. Inhibition of glucose uptake and oxidation by many body cells
(“insulin antagonism”), but not by the brain.
d. Stimulation of triglyceride catabolism in adipose tissue, with
release of glycerol and fatty acids into the blood.
• Enhanced vascular reactivity (increased ability to maintain
vasoconstriction in response to norepinephrine and other stimuli).
• Unidentified protective effects against the damaging influence of
stress
• Inhibition of inflammation and specific immune responses.
• Inhibition of nonessential functions (eg., reproduction and growth).
Actions of the Sympathetic Nervous system ,
including epinephrine secreted during stress
• Increased hepatic and muscle glycogenolysis (provides a
quick source of glucose).
• Increased breakdown of adipose tissue, tissue triglyceride
(provides a supply of glycerol for gluconeogenesis and fatty
acids for oxidation).
• Decreased fatigue of skeletal muscle.
• Increased cardiac function (eg., increased heart rate).
• Diverting blood from viscera to skeletal muscle by means of
vasoconstriction in the former beds and vasodilation in the
latter).
• Increased lung ventilation by stimulating brain breathing
centres and dilating airways.
Other hormones released during stress
• Aldosterone, vasopressin (ADH), growth
hormone, glucagon, and beta-endorphin
coreleased with ACTH,
• Overall effects of changes in GH, glucagon
and insulin, like those of cortisol and
epinephrine, to mobilise energy stores
• Chronic stress can have deleterious
effects
Different types of stress that increase
cortisol release
•
•
•
•
•
•
Trauma of any type
Infection
Intense heat or cold
Injection of norepinephrine
Surgery
Any debilitating disease
CLINICAL CORRELATES
• Enzyme deficiencies
• Adrenal insufficiency
• Excessive production of adrenocortical
hormones
ENZYME DEFICIENCIES
• Deficiency of desmolase is fatal
• Deficiencies of other enzymes cause low
cortisol secretion and congenital adrenal
hyperplasia
DEFICIENCY OF 3B HYDROXYLASE
• Increased DHEA
• Some masculinisation
• Hypospadias (congenital condition in
males in which the opening of the urethra
is on the underside of the penis)
17 A Hydroxylases
• Female genitalia present
• Increased levels of mineralocorticoids
• Decreased levels of cortisol but partially
compensated by corticosterone
21 B hydroxylase
• Gene is on chromosome 6 (HLA)
• Most common deficiency (90%)
• Decreased production of cortisol and
mineralocorticoids
• Increased androgens will cause
virilisation
• Salt losing form
11 B hydroxylase
•
•
•
•
Virilisation
Increased 11 deoxy’s
Water retention
hypertension
VIRILISATION
•
•
•
•
•
•
•
Hirsutism
Baldness (receeding hairline)
Androgenic flush
Small breasts
Male escutchen
Enlarged clitoris
Heavy arms
Baby with CAH
Adrenal insufficiency
• This is due to destruction of the adrenal
gland
• This can be due TB, meningococcemia,
autoimmune destruction of gland
(Addison’s disease)
• This results in low levels of cortisol and
aldosterone
FEATURES OF THE CONDITION INCLUDE
•
•
•
•
•
Weakness, lethargy and Loss of appetite
Hypotension
Low blood glucose
Inability to cope with stress
Hyperpigmentation (due to MSH activity
of ACTH)
TESTS FOR ADRENAL CORTICAL
FUNCTION
• Estimation of free and unaltered levels of
cortisol in urine
• Urinary excretion of 17 hydroxysteroids
(NR = 2 – 12mg/day)
• Dexamethasone suppression test
• Adminstration of metyrapone which
inhibits cortisol secretion and measuring
ACTH levels
• Measurement of aldosterone levels
• 17 ketosteroids for sex steroids
Hypoadrenalism (Addison’s disease)
• This is due to insufficient adrenocortical
hormones
• Most common cause is primary atrophy or
injury, tuberculous destruction of the
gland or cancer
• Disturbances cause mineralocorticoid
deficiency, Glucocorticoid deficiency and
melanin pigmentation
Features of Addison’s disease
Addison’s disease
• Mineralocorticoid deficiency
– Results in loss of sodium ions, chloride ions and causes
water to be lost into urine
– This results in hyponatremia,hypercalemia and mild
acidosis
– Plasma volume falls, cardiac output and blood pressure
decreases and patient dies in shock
• Glucocorticoid deficiency
– No proper synthesis of glucose, reduced mobilization of
proteins and fats
• Melanin pigmentation
– Melanin pigmentation of mucous membrane and skin
– Melanin deposited in blothes in thin areas of the skin due
to increased sectretion of MSH
Hyperaldosteronism
Potassium depletion, sodium retention
Weakness without e0dema
Hypertension, tetany, hypokalaemic alkalosis
Polyuria
It can be primary (Conn’s Syndrome) or
secondary (cirrhosis,Heart
Failure,Nephrosis)
• In secondary hyperaldosteronism there is
eodema and the renin concentration is low
•
•
•
•
•
Hyperadrenalism- Cushing’s syndrome
Hypercorticolism can occur due to• Adenomas of the anterior pituitary secreting
increased ACTH
• Abnormal function of hypothalamus causing
increased CRH and thereby increased ACTH
• Adenomas of the adrenal cortex
When cushing’s syndrome is secondary to
excess secretion of ACTH by the anterior
pituitary this is called Cushing’s disease
Escape Phenomenon
• In cases of hyperaldosteronism, there is
increased fluid retention
• However, fluid retention will lead to stretch
of the right atria
• This will lead to release of ANP which
inhibits release of renin and also has
opposite effects to those of ATII and
aldosterone
• This will then lead to loss of fluid despite
high levels of aldosterone (hence body
escapes the effects of aldosterone
Cushing’s syndrome
Adrenal Medulla
•
•
•
•
•
•
The secretions from the medulla include
- catecholamines (E, NE, Dopamine)
- opioids (met enkephalins)
Adrenomedullin
ATP, Chromogranin A
The major output hormone of the gland
is epinephrine
Phenylethanolamine N-methyltransferase (PNMT)
• Is found in the adrenal medulla and brain
• It is induced by glucocorticoids
• Glucocorticoids are also important for
normal medulla growth and development
• Catecholamines have a half life of two
minutes
• They are metabolised by COMT and MAO
(Catechol-O-methyltransferase, LMonoamine oxidases)
• Increased glycogenolysis in liver and
muscle
• Mobilisation of FFAs
• Increased plasma lactate
• Increase in BMR
• Increased rate and force of contraction
• Increased myocardial excitability
• Increased secretion of insulin and glucagon
Catecholamines
Noepinephrine
• Vasoconstriction
• Hypertension
• - reflex bradycardia
• - Cardiac output falls
• - increased alertness
Epinephrine
• Vasodilatation
• Widens pulse pressure
• Increases cardiac output
and increases cardiac
rate
• Anxiety and fear
Dopamine
• Renal vasodilatation and dilation of
mesenteric vessels
• Positive ionotropic effect
• Increases systolic pressure and no
change in diastolic
• Natriuresis, inhibit Na pump
• It is useful in the treatment of traumatic
and cardiogenic shock
Regulation of secretion
•
•
•
•
•
•
•
The following increase secretion
- cold
- hypoglycemia
- Surgery/ anaesthesia
- emotional excitement
- familiar emotional stress (NE usually)
- unfamiliar emotional stress ( E)
PHEOCHROMOCYTOMA
• Adrenal medullary tumour
• Secretes epinephrine or norepinephrine
producing sustained hypertension
• Secretion can however be episodic
producing intermittent bouts of
palpitations, headache, glycosuria and
extreme systolic hypertension
ENDOCRINE PANCREAS
Objectives
• List the hormones that affect the plasma glucose
concentration and briefly describe the action of each
• Describe the structure of the pancreatic islets and name the
hormones secreted by each of the cell types in the islets
• Describe the structure of insulin and outline the steps
involved in its biosynthesis and release into the bloodstream
• List the consequences of insulin deficiency and explain how
each of these abnormalities is produced
• Describe insulin receptors, the way they mediate the
effects of insulin, and the way they are regulated
• Describe the types of glucose transporters found in the body
and the function of each
• List the major factors that affect the secretion of insulin
Anatomy
Pancreas
• Pancreas has an exocrine portion (80%),
B islets (2%) and ducts + blood vessels
make up the remainder.
• 1- 2 million islets with copius blood
supply
STRUCTURE OF ISLET OF LANGERHANS
Endocrine pancreas
• Insulin (storage) and glucagon (catabolic)
are involved in the regulation of
carbohydrate metabolism
Insulin
• Insulin is a polypeptide containing 2 chains of
Aas linked by disulfide bridges
• Gene for insulin is located on short arm of
chromosome 11
• Normally 90 – 97% of product released from B
cells is insulin and equimolar amounts of C
peptide
• The rest is mainly proinsulin
• C peptide can be measured by RIA and its
levels provides an index of B cell function
Insulin metabolism
• Average amount of insulin secreted a day
is 40IU
• Half life of insulin is about 5 minutes
• It binds to receptors and it is internalised
• Destroyed by proteases in the endosomes
formed by endocytotic process
• Insulin receptor is a tyrosine kinase
MECHANISM OF ACTION
Effects of insulin-Liver
Decreased ketogenesis
Increased protein synthesis
Increased lipid synthesis
Decreased glucose output due to
decreased gluconeogenesis,
• Increased glycogen synthesis, and
increased glycolysis
•
•
•
•
Effects if insulin-Adipose tissue
Increased glucose uptake
Increased FFA synthesis
Increased glycerol phosphate synthesis
Increased triglyceride deposition
Activation of LPL and inhibition of
hormone sensitive lipase
• Increased K uptake (increased activity of
Na pump)
•
•
•
•
•
Effects of insulin-muscle
Increased glucose entry
Increased glycogen synthesis
Increased amino acid uptake
Increased protein synthesis in ribosomes
Decreased protein catabolism
Decreased release of gluconeogenic amino
acids
• Increased ketone uptake
• Increased K + uptake
•
•
•
•
•
•
Effects of insulin
• Generally increased growth
• Increase glucose uptake by the brain
Regulation of insulin secretion
• Effects of plasma glucose-major regulator
of insulin secretion
• Glucose enters B cells via GLUT2
transporters
• Glucose is metabolised and ATP is formed
• ATP enters cytoplasm where it inhibits ATP
sensitive K channels, K efflux
• This depolarises B cells and Ca enters cell
via voltage gated Ca channels
• This results in exocytosis and a spike in
insulin secretion
INCRETIN EFFECT
Maximal decline after 30mins if IV administration, 2-3hrs if oral
Factors increasing insulin secretion
• Glucose, mannose, Aas (leucine, arginine)
• Intestinal hormones
(GLP[7-36],CCK,gastrin,etc)
• B ketoacids
• Acetylcholine
• Glucagon
• cAMP, B adrenergic stimulators
• Theophylline
• Sulfonylureas (eg glipizide, chlopropamide)
Factors decreasing insulin secretion
•
•
•
•
•
•
•
•
•
Somatostatin
2 deoxyglucose, mannoheptulose
Alpha adrenergic stimulators
B blockers
Galanine
Diazoxide and thiazide diuretics
Potassium depletion
Phenytoin, alloxan
Insulin and microtubule inhibitors
Glucagon
• Is a polypeptide with 29 AA residues
produced by A cells of pancreas and the
upper GIT
• Post translational processing of
preproglucagon in A and L cells produces
different proteins
• Glucagon has a half life of 5 – 10 minutes
• Degraded by many tissues especially the
liver
Mechanism of action
• Acts through increaseing cAMP and Ca
Action
• Glycogenolytic, lipolytic and ketogenic
• Is positively ionotropic
• Also stimulate release of GH, insulin and
pancreatic somatostatin
Somatostatin
• Made in the δ cells of the pancreatic islets
and also D cells of the gastrointestinal
tract in the hypothalamus, and in several
other sites in the CNS
Somatostatin
• Somatostatin inhibits the secretion of
multiple hormones
– Growth hormone
– Insulin
– Glucagon
– Gastrin
– Vasoactive intestinal peptide (VIP)
– Thyroid-stimulating hormone
Amylin
• Is a 37 amino acid peptide hormone cosecreted with insulin from the β cells of
the pancreas
• Similar signal transduction pathway with
calcitonin
• Physiological
– Inhibits glucagon secretion
– Delays gastric emptying
– Acts as satiety agent
Amylin
• Exhibits physiochemical properties
predisposing the peptide to aggregate and
form amyloid fibres which play a role in
destruction of β-cell destruction in type 2
diabetes
• Amylin analogue pramlintide maybe
beneficial in people with diabetes
Effects of exercise on metabolism
• Exercise causes an insulin independent
increase in the number of GLUT 4
transporters
• What is the effect of exercise then in
people with diabetes?
Effects of other hormones on
carbohydrate metabolism
•
•
•
•
Thyroid hormones
Catecholamines
Glucocorticoids
Growth hormone
Clinical correlates
• Deficiency of insulin (Diabetes Mellitus)
• Excess insulin
• Excess glucagon
DIABETES MELLITUS
Facts about diabetes mellitus
• In 2010 an estimated 285 million people
worldwide had diabetes (International Diabetes
Federation)
• The federation predicts as many as 438 million
will have diabetes by 2030.
• 90% of the present cases are type 2 diabetes
associated with obesity
• Leading cause of renal failure and blindness
worldwide
• Most people with type 2 diabetes do not know it
• Diabetes can be prevented or treated by
lifestyle modification
Diabetes mellitus
• Diabetes mellitus is a metabolic disorder
with heterogenous aetiologies which is
characterised by chronic hyperglycemia
and disturbances of carbohydrate , fat
and protein metabolism resulting from
defects in insulin secretion ,insulin action
or both
Types of diabetes
• It is divided into primary and secondary
DM
– Types of primary DM are
• (i) Type I DM
• (ii) Type II DM
– Secondary DM is due to conditions such as
chronic pancreatitis, Cushing’s Syndrome and
acromegaly
• Gestational diabetes
Gestational diabetes
• Pregnancy is a diabetogenic state
• Develops during the second or third
trimester
• 70 % of women who have had gestational
diabetes will develop T2DM at some point
in their life time (American Diabetes
Association 2013).
Type 1 diabetes mellitus
There is an absolute deficiency of insulin
Typically occur in childhood
Account for 5-10 % of diabetes cases
Usually occurs before 30 years of age but
not always
• 33% concordance rate in twins
• Usually complicated by DKA
•
•
•
•
Type 1 diabetes mellitus
• Is due to an autoimmune disease of
pancreas
• Causes
– Genetic process
– Environmental (viruses , cow milk
consumption at early age)
– Lack of vitamin D
– Autoimmune
Type 2 diabetes mellitus
• Relative deficiency of insulin, resistance to
insulin
• Common after the age of 40 (maturity onset)
• There are several genetic defects described
including defects in glucokinase, insulin,
insulin receptor, GLUT 4 or IRS 1
• Concordance rate in twins is 50%
• Not complicated by DKA but by hyperosmolar
non ketotic coma
Symptoms of diabetes
•
•
•
•
•
Increased urination(polyuria)
Increase thirst/dry mouth(polydipsia)
Increased hunger (polyphagia)
Fatigue and weakness
Frequent infections
Symptoms of diabetes
•
•
•
•
Poor wound healing
Blurred vision
Weight loss
Yeast infections and fungal skin infections
occur more frequently
Management of DM
• Involves diet and drugs
• Type 1 is managed using recombinant
insulin
• Type 2 is managed using diet, drugs and/
or insulin
• Drug classes include sulfonylureas,
thiazolidinediones, biguanides, GLP
agonists (exanatide), peptide antagonists (gliptines)
Complications of DM
• Microvascular Abnormalities
– Retinopathy
– Nephropathy
– Diabetic neuropathy)
• Macrovascular abnormalities
– Coronary artery disease
– Peripheral vascular disease
– Cerebrovascular disease
SORBITOL
Sorbitol pathway
• The pathophysiology can be explained by
– (i) The sorbitol pathway (inhibition of the Na
pump)
– (ii) Non enzymatic glycation
– Amadori products
– Advanced glycation end products (AGEs) eg
Hb1Ac and fructosamine
• These can be used in the assessment of
long term glucose control
• Most feared complication by people with
diabetes
• Hypoglycemia may manifest during sleep
• Hypoglycaemia is recognised when blood
glucose concentration fall to < 4 mmol /L
• Severe hypoglycaemia may lead to
permanent neurological damage or brain
death and maybe responsible for sudden
death (death in bed syndrome)
– Inappropriate insulin or sulfonylurea overdose
– Decreased food intake-missed meals or small
or late meals
– Strenuous exercise or unplanned activity
– Alcohol intake
– Progressive renal failure causing decreased
renal clearance of insulin
• Treatment involves replacing glucose and
treatment of underlying conditions