Need for Dialysis

Mirasol, Jason M.

Diabetic
Neuropathy

Mirasol, Jason M.

COMPLICATIONS of CKD
Secondary to
Diabetic Nephropathy

Diabetic
Retinopathy

Antonio, Neil Brian B.

Diabetic Vascular
Disease

Berco, Arlyn M.

Coronary Artery
Disease
Orcini, Ve R.

Hyperglycemic
Hyperosmolar
State
Padrinao, Jimmy R.

2014
In Partial Fulfilment
of the Requirements
for Nephrology

Submitted to:
Dr. R. Valenzona

Need for Dialysis

by: Jason M. Mirasol
The kidneys function to remove waste products from the blood. Sometimes this filtering system breaks
down. Diabetes can damage the kidneys and cause them to fail. Failing kidneys lose their ability to filter
out waste products, resulting in kidney disease. High levels of blood sugar make the kidneys filter too
much blood. All this extra work is hard on the filters. After many years, they start to leak and useful
protein is lost in the urine.
In time, the stress of overwork causes the kidneys to lose their filtering ability. Waste products then
start to build up in the blood. Finally, the kidneys fail. This failure, ESRD, is very serious. A person with
ESRD needs to have a kidney transplant or to undergo dialysis.

Diabetic Neuropathy
by: Jason M. Mirasol
Diabetic neuropathy is a peripheral nerve disorder caused by diabetes or poor blood sugar control. The
most common types of diabetic neuropathy result in problems with sensation in the feet. It can develop
slowly after many years of diabetes or may occur early in the disease. The symptoms are numbness,
pain, or tingling in the feet or lower legs. The pain can be intense and require treatment to relieve the
discomfort. The loss of sensation in the feet may also increase the possibility that foot injuries will go
unnoticed and develop into ulcers or lesions that become infected. In some cases, diabetic neuropathy
can be associated with difficulty walking and some weakness in the foot muscles. There are other types
of diabetic-related neuropathies that affect specific parts of the body. For example, diabetic amyotrophy
causes pain, weakness and wasting of the thigh muscles, or cranial nerve infarcts that may result in
double vision, a drooping eyelid, or dizziness. Diabetes can also affect the autonomic nerves that control
blood pressure, the digestive tract, bladder function, and sexual organs. Problems with the autonomic
nerves may cause lightheadedness, indigestion, diarrhea or constipation, difficulty with bladder control,
and impotence.
Parameters
Epidemiology

Characteristics of DM Neuropathy
Case
Most common complication of The patient is diabetic
diabetes mellitus
DM affects men and women with Female
equal frequency.
can occur at any age but is more 57 years old
common with increasing age and
severity and duration of diabetes.

Risk Factors

Clinical Manifestations
History
Sensory manifestations

Motor manifestations
Physical Examination
Sensory

Poor glycemic control

Advanced age
Long duration of DM
Hypertension

feelings of numbness or deadness

of both legs and feet

Uncontrolled diabetes
Advanced age
Long standing DM
Uncontrolled
hypertension

Patient cannot feel her

legs and feet

proximal and distal weakness of Patients legs and feet are

the lower extremities
weak.
decrease or loss of vibratory and
pinprick sensation over the toes

Patient cannot detect the

vibrations from the tuning
fork or distinguish dull or
sharp.
DTRs are not elicited

deep tendon reflexes

commonly hypoactive or absent.

Motor

proximal and distal weakness of Patient cannot move her

the lower extremities
lower extremities

Discussion
Neuropathies are the most common complication of diabetes mellitus (DM), affecting up to 50% of
patients with type 1 and type 2 DM. Patients with type 2 diabetes mellitus may present with distal
polyneuropathy after only a few years of known poor glycemic control; sometimes, these patients
already have neuropathy at the time of diagnosis.
In our case, the patient has no strict compliance to her anti-hyperglycemic medications. Consequently,
the above symptoms were noted together with a group of comorbid conditions. And because of her
many risk factors, it is more probable for her to manifest with such complications.
Pathophysiology
Hyperglycemia causes increased levels of intracellular glucose in nerves, leading to saturation of the
normal glycolytic pathway. Extra glucose is shunted into the polyol pathway and converted to sorbitol
and fructose by the enzymes aldose reductase and sorbitol dehydrogenase. Accumulation of sorbitol and
fructose lead to reduced nerve myoinositol, decreased membrane Na+/K+ -ATPase activity, impaired
axonal transport, and structural breakdown of nerves, causing abnormal action potential propagation.
This is the rationale for the use of aldose reductase inhibitors to improve nerve conduction.

Complications of Diabetic Neuropathy

Once the patient has develop diabetic neuropathy, clinicians should be very cautious because this can
cause a number of more serious complications, including:
1. Loss of a limb- Because nerve damage can cause a lack of feeling in your feet, cuts and sores
may go unnoticed and eventually become severely infected or ulcerated a condition in which
the skin and soft tissues break down. The risk of infection is high because diabetes reduces
blood flow to your feet.
Infections that spread to the bone and cause tissue death (gangrene) may be impossible to treat
and require amputation of a toe, foot or even the lower leg.
2. Charcot joint- This occurs when a joint, usually in the foot, deteriorates because of nerve
damage. Charcot joint is marked by loss of sensation, as well as swelling, instability and
sometimes deformity in the joint itself.
3. Urinary tract infections and urinary incontinence- Damage to the nerves that control your
bladder can prevent it from emptying completely. This allows bacteria to multiply in your
bladder and kidneys, leading to urinary tract infections. Nerve damage can also affect your
ability to feel when you need to urinate or to control the muscles that release urine.
4. Low blood pressure- Damage to the nerves that control circulation can affect your body's ability
to adjust blood pressure. This can cause a sharp drop in pressure when you stand after sitting
(orthostatic hypotension), which may lead to dizziness and fainting.

Treatment
The goal of treating diabetic neuropathy is to prevent further tissue damage and relieve discomfort. The
first step is to bring blood sugar levels under control by diet and medication. Another important part of
treatment involves taking special care of the feet by wearing proper fitting shoes and routinely checking
the feet for cuts and infections. Analgesics, low doses of antidepressants, and some anticonvulsant
medications may be prescribed for relief of pain, burning, or tingling. Some individuals find that walking
regularly, taking warm baths, or using elastic stockings may help relieve leg pain.
Prognosis
The prognosis for diabetic neuropathy depends largely on how well the underlying condition of diabetes
is handled. Treating diabetes may halt progression and improve symptoms of the neuropathy, but
recovery is slow. The painful sensations of diabetic neuropathy may become severe enough to cause
depression in some patients.

References:
Carrington AL, Litchfield JE. The aldose reductase pathway and nonenzymatic glycation in the
pathogenesis of diabetic neuropathy: a critical review for the end of the 20th century. Diabetes
Reviews. 1999.;7:275-99.
Greene DA, Arezzo JC, Brown MB. Effect of aldose reductase inhibition on nerve conduction and
morphometry in diabetic neuropathy. Zenarestat Study Group. Neurology. Aug 11 1999;53(3):580-91.
American Academy of Neurology; Diabetic Neuropathy; American
http://patients.aan.com/disorders/index.cfm?event=view&disorder_id=907

Brain

Foundation;

American Diabetes Association; How Does Diabetes Cause Kidney Disease?; Diabetes Forecast
Magazine; December 10, 2013; http://www.diabetes.org/living-with-diabetes/complications/kidneydisease-nephropathy.html

Diabetic Retinopathy
by: Neil Brian B. Antonio
Matured Cataract, Diabetic & Hypertensive Retinopathy
Patient M.A. was diagnosed with Diabetes Mellitus type II since 1990 and hypertensive since
1995 with peak blood pressure of 160/100 (Stage 2 hypertension, JNC 7); usual blood pressure of
150/90 (stage 1 hypertension, JNC7) with maintenance medication since then, however, with missed
medication that was claimed to be 2 days weekly. Even though with medication and on good
compliance, due to 24 years DM and 19 years HTN stage II (JNC VII), the patient was expected to have
diabetic and hypertensive retinopathy as well as cataract secondary to long standing diabetic
retinopathy. Patient claims gradual blurring of vision on both eyes since 2009 and was prescribed with
Trimetazide dihydrochloride (Vastarel 20) 20 mg tablet for thrice daily after meal with poor compliance
and no improvement on vision of both eyes. During fundoscopic examination of the patient, both ROR
shows negative result due to mature cataract on presentation, however, we could not totally rule out
the possibilities of pathology in the retina and highly considered it since the patient has high risk unless
and we can only visualized the retina after phacoemulsification surgery has been done. Diabetic
retinopathy and Hypertensive retinopathy that may be part of the complication of the patient may be
asymptomatic at initial presentation, but the manifestation of retinal disease may be masked by the lens
problem which is matured cataract secondary to diabetes mellitus.

Patient MA
Epidemiology in
Philippines

Diagnosed DM II (24
years), Stage II HTN (JNC
VII) (19 years) , resides in
Bian, Laguna which may
be part of 24% shown in
studies
with
DM
retinopathy in Luzon other
than Metro, Manila with
34% in Study by Diabetes
Center of the Philippines
1
August 30, 2014

57 year-old

HPI

Physical
Examination

with gradual BOV, O.U.

since 2009

160/90mmHg (right arm

supine); peak BP of
160/100
(Stage
2
hypertension, JNC 7);
usual BP of 150/90 (stage
1 hypertension, JNC7)
with
maintenance

Cataract in DM

Diabetic Retinopathy

(1996 1998)a total of

1269 diabetics from 45
hospitals and diabetes
clinics
nationwide
were screened by
ophthalmologists for
cataract and diabetic
retinopathy
using
fundoscopic
examination
fundoscopic tests, 49%
had abnormal eye
findings; 28% with
diabetic retinopathy
(DR); and 28% with
cataract
2-fold in 5-year
incidence of cortical
cataract in Impaired
2
Fasting Glucose (IFG)
Incident
posterior
subcapsular
(PSC)
cataract was more
frequent
among
2
persons with diabetes
3-4x
cataract
prevalaence with DM
under the age of 65
which
may
be
applicable
to
our
patient at 57 year-old
and with 2x excess
prevalence beyond 65
year-old and the most
frequently seen type of
cataract is age-related
or senile cataract
which tends to occur
earlier and progress
more rapidly than
3
nondiabetic patient
with gradual blurring
of vision usually both
eyes

fundoscopic tests,
49% had abnormal
eye findings; 28%
with
diabetic
retinopathy
(DR);
Out of 28% with DR
22% were in the
background stage,
6%
were
in
preproliferative and
1
proliferative stages

pupils are usually mid

dilated 4-5 mm equally
non-reactive to light;
patient
may
see
clearer on peripheral
vision
in
nuclear
cataract making visual

with
gradual
blurring of vision
usually both eyes,
but may also be
sudden if present
with active bleeding
or
vitreous
hemorrhage
pupils are usually 34
mm
equally
equally reactive to
light in the absence
of
cataract
or
pathology that
visual acuity

Hypertensive
Retinopathy
No data available

with
gradual
blurring of vision
usually both eyes

pupils are usually

3-4 mm equally
equally reactive to
light in the absence
of cataract or
pathology that
visual acuity

medication
Pupils are round measuring 4
mm, symmetrical, both non-
reactive to light. Intact VF
and intact EOM

field
intact
but
decreased
VA usually decreased
depending on type of
cataract and maturity
of cataract
mature cataract will
Visual acuity 20/400 on obscured light flow
both eyes
directly
to
retina
showing dark or hazy
media
Fundoscopic : No ROR, hazy
media on both eyes

VA usually to
20/200 or more

VA usually to
20/200 or more

DM retinopathy in
the absence of
cataract in early
stage may show
ROR
since
no
obstruction of light
towards
the
vascular
choroid
passing
through
transparent retina
but
may
show
sudden BOV once
positive
vitreous
hemorrhage

Hypertensive
retinopathy in the
absence of cataract
in early stage may
show ROR since no
obstruction of light
towards
the
vascular
choroid
passing
through
transparent retina
but may suddenly
decreased
if
positive ruptured
blood vessels

References:
1. Diabetic Retinopaties in Filipinos, Philippine Center for Diabetes Education issued last August 30, 2014;
http://www.diabetescenter.org.ph/
2. http://www.ncbi.nlm.nih.gov/pubmed/15512989
3. Journal of Ophthalmology: Diabetic Cataract, Article ID 608751, Schmidt-Erfurth, et. al., 2010

Pathophysiology of DM Retinopathy

Actually, the exact mechanism by which diabetes causes retinopathy remains unclear, but
several theories have been postulated to explain the typical course and history of the disease. Growth
hormone in the form of VEGF; platelet and blood viscosity; aldose reductase and vasoproliferative
factors may contribute to the pathophysiology. Growth hormone appears to cause the development and
progression of diabetic retinopathy. While increased erythrocyte aggregation, decreased red blood cell
deformability, increased platelet aggregation, and adhesion, predispose the patient to sluggish
circulation, endothelial damage, and focal capillary occlusion leads to retinal ischemia, which, in turn,
contributes to the development of diabetic retinopathy. Increased levels of blood glucose are thought to
have a structural and physiologic effect on retinal capillaries causing them to be both functionally and
anatomically incompetent. A persistent increase in blood glucose levels shunts excess glucose into the
aldose reductase pathway in certain tissues, which converts sugars into alcohol like glucose into sorbitol,
galactose to dulcitol. Intramural pericytes of retinal capillaries seem to be affected by this increased
level of sorbitol, eventually leading to the loss of their primary function like autoregulation of retinal
capillaries. Resulting in weakness and eventual saccular outpouching of capillary walls leading to
microaneurysms, which are the earliest detectable signs of DM retinopathy that may be seen on patient
once the cataract, has been extracted.

Pathophysiology of Cataract in Diabetic Patient

Diabetic cataract is not yet fully understood, however, attributed to enzyme aldose reductase
(AR) which catalyzes the reduction of glucose to sorbitol through the polyol pathway in the initiation of
the disease process. It has been shown that the intracellular accumulation of sorbitol leads to osmotic
changes resulting in hydropic lens fibers that degenerate and form sugar cataracts. In the lens of the
patient, sorbitol is produced faster than it is converted to fructose by the enzyme sorbitol
dehydrogenase. The polar character of sorbitol prevents its intracellular removal through diffusion. The
increased accumulation of sorbitol creates a hyperosmotic effect that results in an infusion of fluid to
countervail the osmotic gradient. Intracellular accumulation of polyols leads to a collapse and
liquefaction of lens fibers, which ultimately results in the formation of lens opacities that was evident of
handheld ophtalmoscope during eye examination in the ward.The Osmotic Hypothesis of sugar
cataract formation, emphasizing that the intracellular increase of fluid in response to AR-mediated
accumulation of polyols results in lens swelling associated with complex biochemical changes ultimately
leading to cataract formation. In study by Framingham published in Journal of Ophthalmology 2010
article ID 608751 cited in study by Schmidt-Erfurth in Medical University Vienna in Austria, they
mentioned 3-4x increased cataract prevalaence with DM under the age of 65 which may be applicable to
aou patient at 57 year-old and with 2x excess prevalence beyond 65 year-old and the most frequently
seen type of cataract is age-related or senile cataract which tends to occur earlier and progress more
rapidly than nondiabetic patient. They also mentioned 10 year cumulative incidence in DM type II of
24.9%.

Hypertensive Retinopathy on top of Diabetic Retinopathy

The findings of hypertensive retinopathy in this patient can also be seen only after cataract
extraction that may visualized the retina on fundoscopic examination, however, B-scan may be helpful
only when vitreous hemorrhage is present and hypertension induced changes to the retinal
microvasculature. Hypertension leads to a deposition of cholesterol into the tunica intima of medium
and large arteries. This leads to an overall reduction in the lumen size of these vessels. In
arteriolosclerosis, hypertension leads to focal closure of the retinal microvasculature that may be
aggravated by diabetic retinopathy leading to early microaneurysms. This may also gives rise to
microinfarcts (cotton wool spots) and superficial hemorrhages. It can also lead to disc edema.The
mechanism behind this phenomenon is also poorly understood like the two conditioned mentioned
above in this patient, but it may be related to a hypertension-related increase in intracranial pressure,
and hence is considered true papilledema. Again, this may only be seen once the cataract has been
extracted in patient M.A. The arteriolosclerotic changes in the retinal microvasculature persist even with
the reduction of systemic blood pressure. However, hypertensive retinopathy changes resolve over time
with the reduction of systemic blood pressure (BP). Cotton wool spots develop in 24 to 48 hours with
the elevation of BP and resolve in two to 10 weeks with the lowering of BP. A macular star develops
within several weeks of the development of elevated BP and resolves within months to years after the
BP is reduced. Papilledema develops within days to weeks of increased BP and resolves within weeks to
months following BP lowering, that is why if only due to hypertension alone excluding cataract and
diabetic retinopathy the vision may be fluctuating, however, what is evident in the patient at this point
is the effects of cataract that cause gradual blurring of visual acuity of 20/400 on both eyes, negative
ROR and hazy media.

References:
Clinical Ophthalmology: A Systematic Approach by Kanski 7th Ed.
Journal of Ophthalmology: Diabetic Cataract, Article ID 608751, Schmidt-Erfurth, et. al., 2010
Images from www.medscape.com

Diabetic Vascular Disease

by: Arlyn M. Berco

Parameters

Diabetic Vascular Disease

Epidemiology

Most common causes of

mortality and disability of
diabetic patients
Affects men and women,
more common in elderly

Risk factors

Environmental and genetic

factors
Advanced age
Diabetes Mellitus
Dyslipidemia
Hypertension
Hypercoagulable state

Clinical Manifestations
History

Physical exam
Cardiovascular

Patient has long standing

hypertension and diabetes
Left ventricular hypertrophy

Case
Female
54 years old
Hypertensive for 19 years
Diabetic for 24 years
Menopause at age 54
54 years old
Long diabetes mellitus
BP of 150/90
Poor medical compliance
Uncontrolled hypertension

Patient can feel dizziness and

light headedness
Easy Fatigability
Lateral displacement of apical
beat into anterior midaxillary
line.

Discussion
Diabetes mellitus affects approximately 100 million persons worldwide. Five to ten percent have type 1
(formerly known as insulin-dependent) and 90% to 95% have type 2 (noninsulin-dependent) diabetes
mellitus. The incidence of type 2 diabetes arises due to lifestyle patterns contributing to obesity. In fact,
Vascular diseases are the principal causes of death and disability in people with diabetes.
Pathophysiology
In patients with diabetes, atherosclerosis is the main reason on impairment of vascular component.
Endothelial cells present on the blood vessel wall normally maintain the vascular homeostasis , ensuring
adequate blood flow and nutrient delivery while preventing thrombosis and leukocyte diapedesis.
Endothelial cells synthesized nitric oxide (NO) to promote vasodilation by activating guanylyl cyclase on
vascular smooth muscle to protect blood vessels to form endogenous injury. In addition, overproduction
of reactive oxygen species (ROS) as a result of altered glucose metabolism together with decrease on

NO will permit the activity of pro inflammatory transcription factor B (NFB) leading to leukocyte
adhesion and production of cytokines and chemokines. In combination with endothelial cell insulin
resistance, these changes cause endothelial dysfunction. This will promote the monocyte and smooth
muscle migration into the intima forming macrophage foam cells. Proliferating vascular smooth muscle
cells are the major source of extracellular matrix in the atherosclerotic plaque and to the fibrous cap
covering the plaque, result in obstructed blood flow leading to diminished amounts of oxygen and
nutrients reached the target organ. Metalloproteinases released by macrophage cells will cause the
breakdown of fibrous cap and causes plaque rupture. The Exposed necrotic core and other extracellular
components to circulating blood will precipitate the major life-threatening events in atherosclerosis,
including myocardial infarction and stroke.
Complications of Vascular Diabetes
Heart disease
Damage to the heart muscle, leading to impaired relaxation and filling of the heart with blood (diastolic
dysfunction) and eventually heart failure; this condition can occurs independent of damage done to the
blood vessels over time from high levels of blood glucose.
Stroke
Long standing diabetes more likely to have a stroke due to its vascular damaged done by the disease.
Plaque buildup and clot formation cause blockage in the blood vessels leading to the brain.
Peripheral arterial disease
Patients with diabetes are at risk for narrowing of the large vessels of their legs. The resulting poor
circulation impairs healing and means that even a minor injury or infection can develop into a serious
infection. A serious foot infection may travel up your leg, infect the bones, and may lead to an
amputation.

Macrovascular complications and their symptoms

Complication
Heart disease

Symptoms
Chest pain or a feeling of squeezing/pressure. If you have
autonomic diabetic neuropathy, you may not have chest pain.
Decreased tolerance for physical activity
Chronic fatigue
Shortness of breath
Swelling of the legs and ankles
Palpitations

Stroke

Impaired speech
Inability to see in one eye or double vision
Inability to walk
Paralysis on one side of the body
Numbness or tingling

Peripheral arterial disease

Pain in the calves when walking

Coolness of the lower extremities
Loss of hair on the legs
Ulcers on the legs that do not heal promptly
Pain in the feet when resting

References
Christian Rask-Madsen, George L. King. Vascular Complications of Diabetes: Mechanisms of Injury and
Protective Factors. Cellular metabolism Volume 17, Issue 1, 8 January 2013, Pages 2033.
Healthwise
Staff
(Sep.
3,
2013)
Macrovascular
Diabetes
complications.
https://myhealth.alberta.ca/health/Pages/conditions.aspx?hwid=uq1204abc 1995-2014 Healthwise,
Incorporated.

Coronary Artery Disease

by: Ve R. Orcini
Parameters
Epidemiology

Risk Factors

Clinical Manifestations
History

Physical Examination

Coronary Artery Disease

Of particular significance in
Developing Countries
African or Asian ancestry
Greatly affects men than
pre-menopausal women.
But
once
past
the
menopause, CAD affects
both similarly.

Type2diabetes
Hyperlipidemia
Advanced age
High blood pressure
(hypertension)
Physical inactivity
Low socio-economic
status

Shortness of breath
Dizziness
Nausea
Feeling very tired

Hypertension
Poor cardiac output
Left ventricular
hypertrophy (LVH)

Case
Filipino
Female
Menopause at 54 yrs. old.

Long standing DM type 2

57 yrs. old
usual blood pressure of
150/90
No routine exercise daily

Orthopnea (2- pillow)

Dizziness
Light headedness
Easy Fatigability
Body malaise

BP: 160/90mmHg
CRT of >2 seconds
3cm apex beat visible and
palpable at 5th ICS, left
anterior axillary line

Discussion
CAD is the most common type of heart disease. Coronary artery disease (CAD) accounts for a large
fraction of the morbidity, mortality, and cost of diabetes. Heart diseases and stroke are the No. 1 causes
of death and disability among people with type 2 diabetes. In fact, at least 65 percent of people with
diabetes die from some form of heart disease or stroke. Adults with diabetes are two to four times more
likely to have heart disease or a stroke than adults without diabetes. The American Heart Association
considers diabetes to be one of the seven major controllable risk factors for cardiovascular disease.
Pathophysiology
In diabetes, the predominant form of LDL cholesterol is the small, dense form. Small LDL particles are
more atherogenic than large LDL particles because they can more easily penetrate and form stronger
attachments to the arterial wall, and they are more susceptible to oxidation. Coronary artery disease
occurs when part of the smooth, elastic lining inside a coronary artery (the arteries that supply blood to
the heart muscle) develops atherosclerosis. With atherosclerosis, the artery's lining becomes hardened,
stiffened, and swollen with all sorts of "gunge" - including calcium deposits, fatty deposits, and
abnormal inflammatory cells - to form a plaque.
Complications:
Coronary artery disease can lead to:
Chest pain (angina). When your coronary arteries narrow, your heart may not receive enough blood
when demand is greatest particularly during physical activity. This can cause chest pain
(angina) or shortness of breath.
Heart attack. If a cholesterol plaque ruptures and a blood clot forms, complete blockage of your heart
artery may trigger a heart attack. The lack of blood flow to your heart may damage your heart
muscle. The amount of damage depends in part on how quickly you receive treatment.
Heart failure. If some areas of your heart are chronically deprived of oxygen and nutrients because of
reduced blood flow, or if your heart has been damaged by a heart attack, your heart may
become too weak to pump enough blood to meet your body's needs. This condition is known as
heart failure.
Abnormal heart rhythm (arrhythmia). Inadequate blood supply to the heart or damage to heart
tissue can interfere with your heart's electrical impulses, causing abnormal heart rhythms.
References:
Jeroen J. Bax, MD, PHD, et al. Screening for Coronary Artery Disease in Patients With Diabetes. doi: 10.2337/dc07-9927
Diabetes Care October 2007 vol. 30 no. 10 2729-2736.
Diseases and Conditions. Coronary Artery Disease. Complications.http://www.mayoclinic.org/diseases-conditions/coronaryartery-disease/basics/complications/con-20032038. 1998-2014 Mayo Foundation for Medical Education and Research.
Lanza GA (February 2007). "Cardiac syndrome X: a critical overview and future perspectives". Heart93 (2): 15966.
doi:10.1136/hrt.2005.067330. PMC 1861371. PMID 16399854.
Betsy B. Dokken, PhD, NP, CDE.The Pathophysiology of Cardiovascular Disease and Diabetes: Beyond Blood Pressure and Lipids.
Diabetes Spectrum. July 2008 vol. 21 no. 3:160-165

Hyperglycemic Hyperosmolar State

by: Jimmy R. Padrinao

Diabetic hyperglycemic hyperosmolar syndrome (HHS) is a complication of type 2 diabetes that involves
extremely high blood sugar(glucose) levels without the presence of ketones. Ketones are by products of
fat breakdown. It is a serious condition most frequently seen among older person. It is also usually
brought on something else, such as an illness or infection.
In HHNS, blood sugar levels rise, and your body tries to get rid of the excess sugar by passing it into your
urine. You make lots of urine at first, and you have to go to the bathroom more often. Later you may not
have to go to the bathroom as often, and your urine becomes very dark. Also, you may be very thirsty.
Even if you are not thirsty, you need to drink liquids. If you don't drink enough liquids at this point, you
can get dehydrated.
If HHNS continues, the severe dehydration will lead to seizures, coma and eventually death. HHNS may
take days or even weeks to develop.
Parameters
Epidemiology

HHS
Age(Elderly)
DM affects men and women with equal
frequency.
Common complication of type 2
diabetes mellitus.

Case
M.A. 57y/o Female
Advanced age
The patient is diabetic
Type 2 DM
uncontrolled

Causes

Extremely high blood sugar

Uncontrolled diabetes

Extreme lack of water (dehydration)

Decreased conciousness
Risk Factors
Concurrent illness such as myocardial
infarction or stroke Congestive heart
failure Sepsis, pneumonia, and other
serious
infections,
debilitating
condition.
Limited access to water
Poor kidney function
Poor management of diabetes

Uncontrolled Hypertension
Uncontrolled Diabetes
Patient cannot move her
lower extremities
Patients legs and feet are
weak.
Chronic Kidney Disease
Non-Compliant to her
medications

Physical Findings:

Profound dehydration
Hyperosmolality
and
reveals
hypotension, tachycardia and altered
mental status. Various changes
(complete
lucidity-disorientationlethargy-COMA)
Confusion
Convulsions
Fever
Increased thirst
Increased urination
Lethargy
Weight Loss
Weakness
Nausea
Vomiting
Coma
Dysfunctional movement
Loss of feeling or function of muscles
Speech impairment

Patient had 3 episodes of

non-projectile vomiting
Patient is non- ambulatory
She is chronically ill-looking
and prefers to keep her eyes
closed.
(+) weight loss of 10% in 5
years
(+)Polyuria and Polydypsia
(+)Patients legs and feet are
weak

Discussion:
The prototypical patient with HHS is an elderly individual with type 2 DM, with a several week/years
history of polyuria, weight loss, and diminished oral intake that may culminates mental confusion,
lethargy and coma.
Normally, the kidneys try to make up for high glucose levels in the blood by allowing the extra glucose to
leave the body in the urine. If you do not drink enough fluids, or you drink fluids that contain sugar, the
kidneys can no longer get rid of extra glucose. Glucose levels in the blood can become very high as a
result. The blood then becomes much more concentrated than the normal (HYPEROSMOLARITY).
Hyperosmolarity is a condition in which the blood has a higher concentration of salt (Sodium), glucose
and other substances that normally cause water to move into the bloodstream. This draws the water
out the bodys other organs, including the brain. Hyperosmolarity creates a cycle of increasing blood
glucose levels and dehydration .
Patient M.A. elderly with long standing Diabetes mellitus, non-ambulatory, with a history of vomiting
and chronically ill-looking (prefers to keep her eyes closed) have a higher chance of developing an acute
complication of Diabetes mellitus (Hyperglycemic Hyperosmolar State HHS) .

Pathophysiology
The initiating event in hyperosmolar hyperglycemic state is glucosuric diuresis. Glucosuria impairs the
concentrating capacity of the kidney, further exacerbating water loss. Under normal conditions, the
kidney act as a safety valve to eliminate glucose above a certain threshold and prevent further
accumulation. However, decreased intravascular volume or underlying renal disease decreases the
glomerular filtration rate (GFR), causing the glucose level to increase. The loss of more water than
sodium leads to hyperosmolarity. Insulin is present, but it is not adequate to reduce blood glucose levels
particularly in the presence of significant insulin resistance.
Complication of HHS:
1. Hyperviscosity increases risk of thrombosis
2. Altered mental status
3. Neurologic signs including focal signs such as sensory or motor impairments or focal seizures or
motor abnormalities, including flaccidity, depressed reflexes, tremors or fasciculations.
4. Untreated, will lead to death.
Complications of treatment(HHS):
1. Inadequate treatment Vascular occlusion (e.g. mesenteric artery occlusion, myocardial
infarction, low-flow syndrome and disseminated intravascular coagulopathy) and
rhabdomyolysis.
2. Hyperviscosity increased risk of thrombosis.
3. Overhydration Adult respiratory distress syndrome and induced cerebral edema.

References:
HARRISONS (Principles of INTERNAL MEDICINE 17th EDITION)
Hyperosmolar HyperglycemicNonketotic Syndrome (HHNS) Retrieved 6 July 2012
U.S. Department of Health and Human Services National Institutes of Health
Page last updated: 15 August 2014