Pathophysiologyof Diabetes Mellitus
The pathophysiology of diabetes is related to
the levels of insulin within the body, and the body’s ability to utilize
insulin. There is a total lack of insulin in type 1 diabetes, while in type 2
diabetes, the peripheral tissues resist the effects of insulin.
Normally, the
pancreatic beta cells release insulin due to increased blood glucose
concentrations. The brain in order for normal functions to occur continually
requires glucose.
Hypoglycemia, or low plasma glucose levels, is usually caused
by drugs used in the treatment of diabetes, including insulin and oral
antihyperglycemics.
The pathophysiology of diabetes
involves plasm concentrations of glucose signaling the central nervous system
to mobilize energy reserves. It is based on cerebral blood flow and tissue
integrity, arterial plasma glucose, the speed that plasma glucose
concentrations fall, and other available metabolic fuels.
Low plasma glucose
causes a surge in autonomic activity. Diagnosis of hypoglycemia requires
verification of low plasma glucose levels. Immediate treatment is the intake of
glucose.
The responses to hypoglycemia include decreased insulin secretion,
increased secretion of glucose counter-regulatory hormones such as glucagon and
epinephrine, a greater sympathoadrenal response, related symptoms, and finally,
cognitive dysfunction, seizures, or coma.
Late hypoglycemia of occult
diabetes may develop in some patients with impaired glucose tolerance, or early
type 1 or type 2 diabetes. After a high-carbohydrate meal, the patient
experiences hypoglycemia.
The
epidemiology and pathophysiology of diabetes have
been discussed in previous chapters, as were the major complications of retinopathy, neuropathy,
and nephropathy.
Similar mechanisms underlie complications stemming from the diabetic foot,
including ulceration, gangrene, ischemia,
and, ultimately, amputation. Although glycemic control is
imperative in diabetes, it is not sufficient to eliminate complications of the
diabetic foot.
Furthermore, it is important for clinicians to be aware of the
etiologic triad leading to diabetic foot complications (i.e., neuropathy,
ischemia, and infection) and to recognize that these may occur in isolation but
more frequently occur in combination with one another.
Neuropathy
The
neuropathy stemming from diabetes mellitus has multiple manifestations within
the diabetic foot because it encompasses sensory, motor, and autonomic fibers. Sensory
neuropathy affects small-diameter pain and temperature fibers
first, and susceptibility to injury is increased because these patients are
less sensitive to pressure-related trauma and other minor skin injuries. Motor neuropathy affects
the longer fibers that innervate the foot, including intrinsic foot muscles and
leg muscles.
Atrophy, or muscle wasting,
in the intrinsic foot muscles allows the strong flexor muscles to
draw up the toes in a “clawed” position, and new pressure points emerge at the
tips of the toes and the prominent metatarsal heads. Limited joint mobility and
rigidity from glycation of
scleral proteins exacerbates the situation by further changing the normal
weight distribution on the foot.
Lastly, autonomic
neuropathy causes the skin to become dry through loss of sweat and
apocrine gland function. The resulting dry, scaly skin has a
markedly increased susceptibility to skin breakdown and fissures, thus creating
a portal of entry for bacteria. Additionally, diabetic patients can have a
blunted neuroinflammatory response and thus are missing a crucial component of
the body’s natural first-line defense against pathogens.
Infection
Diabetic patients
typically have an altered response to infectious processes owing to defects in
their host immune defense system. Moreover, wound healing is delayed in
diabetic patients as a result of abnormal cellular and inflammatory pathways
involving fibroblasts, neutrophils,
and advanced
glycation end products (AGEs).
Glycation is a nonenzymatic
chemical reaction whereby sulfhydryl protein
linkages are replaced by glucose, causing impairment in normal cellular and
tissue functions.
AGEs
increase the stiffness of precapillary vessel walls and contribute to the
development of diabetic microangiopathy.
Additionally, the presence of neuropathy
and ischemia can potentiate the infectious process. The loss of protective
sensation from neuropathy leads to unrecognized injury and secondary infection.
Ischemia results
in poor healing, blunts the inflammatory response, and may lead to inadequate
tissue levels of antimicrobial
agents.
Ischemia
Much
progress has been made in identifying the cause of ischemia in the lower
extremities of diabetic patients, and results have challenged long-standing
misconceptions in the literature and in the medical community at large.
It is
imperative that practitioners continue to reject the “small-vessel disease”
theory related to occlusions of the microcirculation,
as espoused by a single histologic study in 1959, and instead embrace the notion that
ischemia results from both atherosclerotic macrovascular
disease and microcirculatory dysfunction. Diabetic
patients typically suffer from tibial and peroneal arterial disease with
sparing of the foot arteries, especially the dorsalis pedis and its branches
Research
has shown that diabetes causes structural and functional changes within the
arteriolar and capillary systems, notably thickening of the basement
membrane. In spite of the thickened capillary
basement membrane, there is no decrease in capillary luminal
diameter. A thickened membrane impairs the migration
of leukocytes and
hampers the normal hyperemic or vasodilatory response to injury, thus
simultaneously increasing the susceptibility to injury while blunting the
typical manifestations of such an injury.
Overall,
this dysfunction of the microcirculation in diabetic patients creates a
functionally ischemic foot despite conditions that would otherwise allow normal
blood flow in healthy patients.
Besides causing
specific structural changes in the microcirculation, diabetes also causes a
compromise in the overall biology of the foot. Diabetes causes
an undesirable shift in the natural balance that exists between
stress/ulceration and resistance to stress/ulceration. Thus, the diabetic foot
is more prone to ulceration from the repetitive low-intensity stress of normal
weight bearing.
The presence of neuropathy may necessitate revascularization under
conditions of perfusion that would not require revascularization in the absence
of neuropathy and is often described as neuroischemia. Because
of the compromise
caused by this neuroischemia, the diabetic foot requires even more perfusion
than usual to resist ulceration or respond appropriately to injury.
Pathophysiology of type 1 diabetes
In this condition the
immune system attacks and destroys the insulin producing beta cells of the
pancreas. There is beta cell deficiency leading to complete insulin deficiency.
Thus is it termed an autoimmune disease where there are anti insulin or
anti-islet cell antibodies present in blood. These cause lymphocytic
infiltration and destruction of the pancreas islets. The destruction may take
time but the onset of the disease is rapid and may occur over a few days to
weeks.
There may be other
autoimmune conditions associated with type 1 diabetes including vitiligo and
hypothyroidism. Type 1 diabetes always requires insulin therapy, and will not
respond to insulin-stimulating oral drugs.
Pathophysiology of type 2 diabetes
This condition is
caused by a relative deficiency of insulin and not an absolute deficiency. This
means that the body is unable to produce adequate insulin to meet the needs.
There is Beta cell deficiency coupled with peripheral insulin resistance.
Peripheral insulin
resistance means that although blood levels of insulin are high there is no
hypoglycaemia or low blood sugar. This may be due to changes in the insulin
receptors that bring about the actions of the insulin.
Obesity is the main
cause of insulin resistance. In most cases over time the patients need to take
insulin when oral drugs fail to stimulate adequate insulin release.
Gestational diabetes is caused when there are excessive
counter-insulin hormones of pregnancy. This leads to a state of insulin
resistance and high blood sugar in the mother. There may be defective insulin
receptors.
Pathophysiology behind symptoms and complications of diabetes
- Polydipsia or increased thirst is due to
high blood glucose that raises the osmolarity of blood and makes it more
concentrated.
- Polyuria or increased frequency of
urination is due to excess fluid intake and glucose-induced urination.
- Weight loss occurs due to loss of
calories in urine.
- Polyphagia or increased hunger due to
loss or excess glucose in urine that leads the body to crave for more
glucose.
- Poor wound healing, gum and other
infections due to increased blood glucose providing a good source of
nutrition to microbes and due to a diminished immunity.
- Heart disease – this occurs due to
changes in the large blood vessels leading to coronary, cerebral, and
peripheral artery diseases, atherosclerosis, dyslipidemia etc.
- Eye damage – this is termed diabetic
retinopathy and occurs due to damage of the fine blood vessels of the
retina in the eye due to long term exposure to high blood sugar.
- Kidney damage – similar damage to small
and large blood vessels of the kidneys. Initially there is proteinuria or
increased outflow of protein and may lead to end stage renal disease
(ESRD).
- Nerve damage – this can affect the arms
and legs and is called stocking-glove numbness/tingling. It can also
affect autonomic functions leading to impotence, erectile dysfunction,
difficulty in digestion or gastroparesis etc.
- Diabetic foot – this occurs due to
peripheral nerve damage as well as blood vessel affliction due to long
term diabetes. Little trauma, sores and blisters go unnoticed due to lack
of sensation and peripheral vascular disease impairs healing and allows
infection.
- Diabetic Ketoacidosis is caused in type
1 diabetes where there is complete lack of insulin and reliance on fatty
acids for energy. This uncontrolled lipid breakdown leads to formation of
ketones and causes acidosis and ketonemia. This is a medical emergency.
- Non-Ketotic Hyperosmolarity – this is
caused due to extreme rise of blood sugar. This is seen in type 2
diabetics. There is just enough insulin to suppress ketone synthesis. The
high blood sugar leads to excessive concentration or osmolarity of blood
which in turn leads to dieresis and collapse of the blood vessels and
cardiovascular shock. This is a medical emergency.
Frequently Asked Question
What is the pathophysiology of type 2 diabetes mellitus?
The pathophysiology of type 2 diabetes mellitus is characterized by peripheral insulin resistance, impaired regulation of hepatic glucose production, and diminishing β-cell function, finally causing toβ -cell collapse.
What is the pathophysiology of diabetes mellitus type 1?
Type 1 DM is the culmination of lymphocytic infiltration and degradation of insulin-secreting beta cells of the islets of Langerhans in the pancreas. As beta-cell mass decreases, insulin secretion reduces until the accessible insulin no longer is sufficient to keep normal blood sugar levels.
What is the basic underlying pathology of diabetes mellitus?
Diabetes mellitus is a syndrome with disordered metabolism and Improper hyperglycemia Because of either a Lack of insulin secretion or into Some combination of insulin resistance and Insufficient insulin secretion to compensate
What is a pathophysiology of a disease?
Pathophysiology is the analysis of these changes of mechanical, physiological, and biochemical functions, possibly caused by a disorder or leading to a strange syndrome. By: Haematology Case Studies with Blood Cell Morphology and Pathophysiology,
What is the pathophysiology of hyperglycemia?
Hyperglycemia results in a reduction in the body's ability to use or store sugar after carbohydrates are consumed and from a rise in the generation of sugar from the liver during the periods between meals.
Post a Comment