Download A chief of endocrinology department, prof. Vlasenko MV

MINISTRY OF HEALTH PROTECTION OF UKRAINE
Vynnitsa national medical university named after M.I.Pyrogov
«CONFIRM»
on methodical meeting of
endocrinology department
A chief of endocrinology
department, prof. Vlasenko M.V.
_________________
“_31_”_august___ 2012 y
METHODOLOGICAL RECOMMENDATIONS
FOR INDEPENDENT WORK OF STUDENTS
BY PREPARATION FOR PRACTICAL CLASSES
Scientific discipline
Мodule № 1
substantial module №1
Topic
Course
Faculty
Internal medicine
Basis of Internal medicine
“Diagnostic, treatment and prophylactic basis of
main endocrinology diseases”
Topic №7: Comas in the patient with diabetes mellitus.
Ketoacidosis. Diabetic ketoacidotic coma: pathogenesis,
clinics, diagnostics, treatment. Hypoglycemic coma:
pathogenesis, clinics, diagnostics, treatment. Concept about
hyperosmolar and lactatacidotic comas. Features of comas in
the children with diabetes mellitus.
4
Medical № 1
Vynnitsa – 2012
METHODOLOGICAL RECOMMENDATIONS
for the students of 4-th course of medical faculty for preparation to the practical
classes from endocrinology
1.Тopic №7: Comas in the patient with diabetes mellitus. Ketoacidosis. Diabetic ketoacidotic
coma: pathogenesis, clinics, diagnostics, treatment. Hypoglycemic coma: pathogenesis,
clinics, diagnostics, treatment. Concept about hyperosmolar and lactatacidotic comas.
Features of comas in the children with diabetes mellitus.
2. Relevance of topic: Diabetic emergencies are dangerous acute complications of Diabetes
Mellitus. Contemporary diagnosis and prevention of comas determine tactic and value of treatment
approach. So, this problem stimulates researchers and doctors of different specializations to
improve our knowledge in this topic. Ketoacidosis is the most frequent endocrine emergency seen
by the primary care physician. Mortality rates from 6 – 10 % have been reported. All the
abnormalities associated with ketoacidosis can be traced to an absolute or relative insulin lack,
which develops over the period of several hours or days.
3. Aim of lesson:
- to learn etiology, pathogenesis, diagnostic criteria of diabetic ketoacidosis (DKA), nonketonic
hyperglycemic-hyperosmolar coma (NKHHC), lactoacidosis (LA) and hypoglycemic coma (HC).
- to know how to differentiate symptoms of diabetic ketoacidosis .
- to know how to diagnose hypoglycemic coma.
- to know how to diagnose hyperosmolar state.
- to know how to interpret results of the laboratory assays.
- to know clinical picture, differential diagnosis and frst aid of diabetic emergencies.
- to learn methods of prophylaxis the comas at Diabetes Mellitus.
4. References
4.1. Main literature
1. Endocrinology. Textbook/Study Guide for the Practical Classes. Ed. By Petro M. Bodnar: Vinnytsya: Nova Knyha Publishers, 2008.-496 p.
2. Basіc & Clіnіcal Endocrіnology. Seventh edіtіon. Edіted by Francіs S. Greenspan, Davіd G.
Gardner. – Mc Grew – Hіll Companіes, USA, 2004. – 976p.
3. Harrison‘s Endocrinology. Edited J.Larry Jameson. Mc Grew – Hill, USA,2006. – 563p.
4. Endocrinology. 6th edition by Mac Hadley, Jon E. Levine Benjamin Cummings.2006. –
608p.
5. Oxford Handbook of Endocrinology and Diabetes. Edited by Helen E. Turner, John A. H.
Wass. Oxford, University press,2006. – 1005p.
4.2. Additional literature
6. Endocrinology (A Logical Approach for Clinicians (Second Edition)). William Jubiz.-New
York: WC Graw-Hill Book, 1985. - P. 232-236.
7. Іnternatіonal Textbook of Dіabetes Mellіtus (Ed by R.A. Defronzo, E. Ferrannіnі, H. Keen,
P. Zіmmet. John Wіley & Sons, Ltd. England, 2004. – Vol. 1 – 1100p., Vol. 2 – 1913p.
8. Joslіn’s Dіabetes Mellіtus. Selected Chapters from the 14-th ed. Edіted by C. Ronald Kahn,
et al. Lіppіncott Wіllіams & Wіlkіns, USA, 2006. – 328p. Manual of Endocrinology and
Metabolism (Second Edition)/ Norman Lavin. – Little, Brown and Company.- Boston-New
York-Toronto-London, 1994. - P. 519-527, 561-574.
9. The diabetic foot. 2nd edition. Edited by A.Veves, J.M.Giurini, F.W. LoGerfo (ebs), Humana
Press, Totowa, New Jersey,2006. – 224p.
Basic Level.
1. Pathogenesis of insulin lack.
2. Drugs which can be used in emergency of DM patients with coma.
Students’ Independent Study Program
You should prepare for the practical class using the existing text books and lectures. Special
attention should be paid to the following:
1. Stages of DKA development.
2. Etiology and diagnosis of diabetes ketosis.
3. The clinical forms of duration and diagnosis of DKA.
4. Diagnostic criteria of diabetic ketoacidosis.
5. Diagnostic criteria of hyperosmolar coma.
6. Diagnostic criteria of lactic acidosis.
7. Diagnostic criteria of hypoglycemic coma.
8. Emergency of DKA.
9. Etiology of NKHHC.
10. Diagnosis of NKHHC.
11. Emergency of NKHHC.
12. Etiology and diagnosis of LA.
13. Emergency of LA.
14. Etiology of HC.
15. Diagnostic criteria of HC.
16. Emergency of HC.
17. Differentiate diagnosis between diabetic emergencies.
Short content of the theme.
Classification of acute complications of DM.
1.
1)
2)
3)
2.
Diabetic coma:
diabetic ketoacidisis (DKA);
nonketonic hyperglycemic-hyperosmolar coma (NKHHC);
lactoacidosis (LA).
hypoglycemic coma (HC).
Diabetic ketoacidisis (DKA).
DKA results from grossly deficient insulin modulation of glucose and lipid metabolism.
Pathophysiology of DKA.
Insulin deficiency
(absolute or relative)
↓ glucose uptake
↑ proteolysis
↑
amino
acides
Hyperglycemia
↑
nitrogen
loss
muscle
breakdown
↑ lipolysis
↑
glycerol
free
fatty
acids
weight loss
↑
ketoge
nesis
Weakness
↑ keton
emia
Gluconeogenesis
+ glucogenolysis
↑ keton
uria
Glucosuria
Osmotic diuresis
Electrolyte depletion
Hypotonic losses
Dehydration and acidosis
Precipitating factors:
1) newly diagnosed diabetes (presenting manifestation);
2) inadequate administration of exogenous insulin;
3) increased requirements for insulin caused by the presence of an underlying stressful condition:
- an intercurrent infection (pneumonia, cholecyctite);
- a vascular disorder (myocardial infarction, stroke);
- an endocrine disorder(hyperthyroidism, pheochromocytoma);
- trauma;
- pregnancy;
- surgery.
Clinical presentation.
Diabetic ketosis.
It is status which is characterized by increased level of ketones in blood, without clinical signs of
dehydration and can be corrected by diet (fat restriction) and regular insulin injection.
DKA develops over a period of days or weeks.
Signs and symptoms.
1. Polydipsia, polyurea and weakness are the most common presenting complaints.
2. Anorexia, nausea, vomiting, and abdominal pain may be present and mimic an abdominal
emergency.
3. Ileus and gastric dilatation may occur and predispose to aspiration.
4. Kussmaul breathing (deep, sighing respiration) is present as respiratory compensation for the
metabolic acidosis and is obvious when the pH is less than 7.2.
5. Symptoms of central-nervous-system involvement include headaches, drowsiness, lassitude,
stupor and coma (only 10 % patients are unconscious).
Physical examination.
1. Hypotermia is common in DKA. A fever should be taken as strong evidence of infection.
2. Hyperpnea or Kussmaul respiration are present and related to degree of acidosis, acetone may
be detected on the breath (musty (fruity) odor to the breath).
3. Tachycardia frequently is present, but blood pressure is usually normal unless profound
dehydration is present.
4. Poor skin tugor may be prominent depending on the degree of hydration.
5. Hyporeflexia (associated with low serum potassium) can be elicited.
6. Signs consistent with a “surgical abdomen” but which follow severe ketonemia can confuse the
clinical picture.
7. In extreme cases of DKA one can see hypotonia, stupor, coma, incoordination of ocular
movements, fied dilated pupils, and finally death.
8. Other signs from a precipitating illlness can be present.
Laboratory findings.
1. The hallmark of DKA is the finding of:
- hyperglycemia;
- ketonemia;
- metabolic acidosis (plasma pH and bicarbonates are decreased.
2. A presumptive bedside diagnosis is justified if the urine is strongly positive for both glucose and
ketones.
3. Different changes of electrolyte levels in the blood can be observed and does not reflect the
actual total body deficits.
4. Serum amylase and transaminases can be elevated.
5. Leucocytosis occurs frequently in DKA and therefore cannot be used as a sole indication of
infectious process.
Types of DKA:
- abdominal;
- vascular collapse;
- cerebral (encephalopathic);
- renal;
- mixed.
Treatment.
The goals of therapy include:
1. Rehydratation.
2. Reduction of hyperglycemia.
3. Correction of: a) acid-base and b) electrolyte imbalance.
4. Investigation of precipitating factors, treatment of complications.
The most important factor to emphasize is the frequent monitoring of the patient both
clinically and chemically. Initially, laboratory data should be obtained every 1 – 3 hours and less
frequently once clinical improvement is noted. If the patient is in shock, stupor or coma, a
nasogastric tube, especially if vomiting, and urinary catheter are recommended.
Frequent assessment of potassium status is vital. A lead II electrocardiogram (ECG) can be
provide a rapid assessment of hyperkalemia (peaked T waves) and hypokalemia (flat T waves and
presence of U waves). Hyporeflexia and ileus are clinical indications of potassium deficiency.
Careful observation of neurological status is vital to detect the infrequent but devastating
presence of cerebral edema.
Rehydration.
The average fluid deficit in adults with DKA is 3 to 5 l. A rapid infusion of 0,9 % sodium
chloride (e.g., 1 l/h for the first 1 to 2 hours) is given and then reduced to about 0,5 – 0,3 l/h if the
blood pressure is stable and the urine follow is adequate. After the initial infusion, intravenous fluid
therapy must be adjusted individually on the basis of urine output, clinical assessments of hydration
and circulation, determination of plasma electrolytes and glucose. When serum glucose level is
about 11 – 13 mmoll/l administration of 5 % glucose with insulin can be performed (1 to 2 unites of
insulin on each 100 ml of 5 % glucose solution). The addition of glucose to the intravenous solution
is necessary for correction of tissue lipolysis and acidosis.
Insulin treatment.
DKA can be treated with low dose insulin regimens; e.g., initial intravenous administration of
10 to 20 units of regular insulin followed by continuous intravenous infusion of 0,1 unit/kg/hour in
0,9 % sodium chloride infusion. (50 units of insulin can be added to a 500 ml bottle of 0,9 %
sodium chloride solution to give 1 insulin unite/10 ml of solution.)
If the glucose level does not improve after an hour of infusion, the rate of insulin is doubled
until a response is noted. But if there is a tendency for decreasing the level of glucemia we have to
decrease the dose of insulin in two times.
When the serum glucose concentration reaches 11-13 mmoll/l, insulin can be given
subcutaneously (if plasma and urine persistently negative for ketones). Blood glucose level should
be maintained at about 11 mmoll/l during intravenous therapy.
Improvement usually is noted in 8 – 24 hours. Following stabilization of the clinical
condition, patients are placed in insulin regimen consisting of five injections of regular insulin.
Treatment of electrolyte disorders.
As a rule, potassium should never be given until the state of renal function is known and until
the serum potassium concentration is available. In most patients the initial serum potassium is highnormal or elevated, and the initiation of K replacement (20 to 40 mmoll/h) usually can be deferred
for 2 hours, using hourly serum measurements as a guide.
Potassium would be to infuse at a rate of ml of 1,5 g/h during 3 – 5 hours.
Correction of metabolic acidosis.
The metabolic acidosis occurs due to insulin deficiency and dehydration. So ketone bodies are
themselves metabolized to bicarbonate once proper therapy is begun (fluids, electrolytes, insulin)
and exogenous administration of bicarbonate can overcorrect to alkalosis.
The use of bicarbonate can be recommended only in the following cases:
- if life-threatening hyperkalemia;
- when severe lactic acidosis complicates DKA;
- with severe acidosis (pH<7), especially when complicated by shock that is not responsive to
appropriate fluid resuscitative measures in an attempt to improve cardiac output.
Bicarbonate would be to infuse at a rate of 100 to 300 ml of 2,5 % solution.
Other therapeutic consideration:
- since infection is one of the leading precipitating events of DKA, it should be looked for and, if
found, treated appropriately;
- vascular thrombosis (it is secondary to severe dehydration, high serum viscosity, and low
cardiac output) – heparin (5000 unites 4 times a day);
- vascular collapse can be treated by mesatone (1 – 2 ml); glucocorticoides (dexametasone 4 mg
two times a day). You must remember that development of vascular collapse after initiation of
therapy should suggest the presence of gram-negative sepsis or silent myocardial infarction;
- cerebral edema (It is a rare and frequently fatal complication. Some physicians believe that
rapid osmotic reduction of plasma glucose should be avoided to minimize rapid osmotic
changes. Some patients have premonitory symptoms (e.g., sudden headache, rapid decrease in
the level of consciousness), but in others acute respiratory arrest is the initial manifestation. If
cerebral edema is diagnosed, therapeutic maneuvers might include the use of : mannitol (1 – 2
g/kg intravenous over 20 min), dexametasone (0,25 – 0,50 mg/kg/day divided q 4 – 6 h). But
they are usually ineffective after the onset of respiratory arrest.
Nonketonic hyperglycemic-hyperosmolar coma (NKHHC or HNC).
HNC is a syndrome characterized by impaired consciousness, sometimes accompanied by
seizures, extreme dehydration, , and extreme hyperglycemia that is not accompanied by
ketoacidosis.
The syndrome usually occurs in patients with type II DM, who are treated with a diet or oral
hypoglycemic agents, sometimes it is a complication of previously undiagnosed or medically
neglected DM (type II).
In contrast to ketoacidosis, mortality in patients with HNC has been very high (50 %) in most
series. Mortality has been associated with convulsions, deep vein thrombosis, pulmonary embolus,
pancreatitis and renal failure. Death is usually due to an associated severe medical condition and not
to the hyperosmolality.
The pathophysiology of HNC is similar to that of ketoacidosis, except that ketoacids do not
accumulate in the blood. The reason of this phenomenon is unclear. Initially it was thought that
patients with HNC produced enough insulin to prevent lipolysis and ketogenesis but not enough to
prevent hyperglycemia. The concept was invalidated by finding similar inappropriately low plasma
insulin concentrations in patients with the two syndromes. The finding of lower plasma free fatty
acids, as well as cortisol and growth-hormone concentrations, in patients with ketoacidosis has
raised the possibility that the absence of ketosis may be the result of decreased cortisol and growthhormone effects on lipolysis. Suppression of lipolysis by hyperosmolality also has been proposed.
HNC usually develops after a period of symptomatic hyperglycemia in which fluid intake is
inadequate to prevent extreme dehydration from the hyperglycemia-induced osmotic diuresis.
PREDISPOSING FACTORS FOR HYPERGLYCEMIC HYPEROSMOLAR STATE
I. Acute illness
– acute infection (32–60 %)
– pneumonia, urinary tract infection, sepsis
– cerebral vascular accident
– myocardial infarction
– acute pancreatitis
– intestinal obstruction
– dialysis, peritoneal
– mesenteric thrombosis
– renal failure
– heart stroke
– hypothermia
– subdural hematoma
– severe burns
– acute pulmonary edema
II. Endocrine
– acromegaly
– thyrotoxicosis
– Cushing’s syndrome
III. Drugs/therapy
– β-Adrenergic blockers
– Calcium channel blockers
– Chlorpromazine
– Cimetidine
– Diazoxide
– Diuretics
– Ethacrynic acid
– Immunosuppressive agents
– L- Asparaginase
– Phenytoin
– Propranolol
– Steroids
– Total parenteral nutrition
– Previously undiagnosed diabetes
–
Predisposing factors.
1. HNC seems to occur spontaneously in about 5 – 7 % of patients.
2. In 90 % of patients some degree of renal insufficiency seems to coexist.
3. Infection (e.g., pneumonia, urinary tract infection, gram-negative sepsis) is underlying frequent
precipitating cause.
4. Use of certain drugs has been associated with this condition:
-
steroids increase glucogenesis and antagonize the action of insulin;
potassium-wasting diuretics (hypokalemia decreases insulin secretion), e.g., thiazides,
furosemide;
- other drugs, e.g., propranolol, azathioprine, diazoxide.
5. Other medical conditions such as cerebrovascular accident, subdural hematoma, acute
pancreatitis, and severe burns have been associated with HNC.
6. Use of concentrated glucose solutions, such as used in peripheral hyperalimentation or renal
dialysis, has been associated with HNC.
7. HNC can be induced by peritoneal or hemodialysis, tube feeding.
8. Endocrine disorders such as acromegaly, Cushing disease, and thyrotoxicosis have also been
associated with HNC.
Clinical presentation.
Signs and symptoms.
1. Polyuria, polydipsia, weight loss, weakness and progressive changes in state of consciousness
from mental cloudiness to coma (present in 50 % of patients) occur over a number of days to
weeks.
2. Because other underlying conditions (such as cerebrovascular accident and subdural hematoma)
can coexist, other causes of coma should be kept in mind, especially in the elderly.
3. Seizures occur in 5 % of patients and may be either focal or generalized.
Physical examination.
1. Severe dehydration is invariably present.
2. Various neurologic deficits (such as coma, transient hemiparesis, hyperreflexia, and generalized
areflexia) are commonly present. Altered states of consciousness from lethargy to coma are
observed.
3. Findings associated with coexisting medical problems (e.g., renal disease, cardiovascular
disease) may be evident.
Laboratory findings.
1. Extreme hyperglycemia (blood glucose levels from 30 mmoll/l and over are common.
2. A markedly elevated serum osmolality is present, usually in excess of 350 mOsm/l. (Normal =
290 mOsm/l). The osmolality can be calculated by the following formula: mOsm/l = 2(Na + K)
= blood glucose/18 + BUN/2.8.
3. The initial plasma bicarbonate averaged.
4. Serum ketones are usually not detectable, and patients are not acidic.
5. Serum sodium may be high (if severe degree of dehydration is present), normal, or high (when
the marked shift of water from the intracellular to the extracellular space due to the marked
hyperglycemia is present).
6. Serum potassium levels may be high (secondary to the effects of hyperosmolality as it draws
potassium from the cells), normal, or low (from marked urinary losses from the osmotic
diuresis). But potassium deficiency exists.
Treatment.
This condition is a medical emergency and the patient should be placed in an intensive care
unit.
Many of the management techniques recommended for a patient with DKA are applicable
here as well.
The goals of therapy include:
- rehydration;
- reduction of hyperglycemia;
- electrolytes replacement;
- investigation of precipitating factors, treatment of complications.
Rehydration.
The average fluid deficit is 10 liters, and acute circulatory collapse is a common terminal
event in HNC. The immediate aims of treatment are to rapidly expand the contracted intravascular
volume in order to stabilize the blood pressure, improve the circulation, and improve the rate of
urine production. It is important to remember that it is the severe hyperglycemia and the
concomitant obligatory shift of water from the intracellular to the intravascular compartment that
prevents this latter space from collapsing at the time of severe fluid depletion. With too rapid a
correction of hyperglycemia, potential hypovolimic shock (as fluid moves from the extracellular
space back into the intracellular space) may occur.
Treatment is starting by infusion 1 to 3 liters of 0,9 % sodium chloride over 1 to 2 hours; if
this suffices to stabilize the blood pressure, circulation and restore good urine flow, the intravenous
fluid can be changed to 0,45 % sodium chloride to provide some free water. 0,45 % sodium chloride
is used at a rate of 150 to 500 ml/hour depending on the state of hydration, previous clinical
response and the balance between fluid input and output. The aim of this phase of intravenous fluid
therapy is not to attempt to rapidly correct the total fluid deficit or the hyperosmolality, but rather to
maintain stable circulation and renal function and to progressively replenish water and sodium at
rates that do not threaten or cause acute fluid overload.
Generally, half of the loss is replaced in the first 12 hours and the rest in the subsequent 24
hours.
Insulin therapy.
Insulin treatment in HNC is started by 10 to 20 unites of regular insulin intravenously as a
bolus dose prior to starting the insulin infusion and then giving intravenously regular insulin in a
dose of 0,05 – 0,10 unites/kg/hour (many authorities routinely use the same insulin treatment
regimens as for treating DKA, other authorities recommend smaller doses of insulin, because they
believe that patients with type II DM are offer very sensitive to insulin, but this view is not
universally accepted, and many obese type II diabetics with NHC require larger insulin doses to
induce a progressive decrease in their marked hyperglycemia. It is important to remember that
because of insulin therapy causes blood glucose levels to fall, water shifts into the cells and existing
hypotension and oliguria can further aggravated. Thus, initially some advocate delaying insulin
therapy while infusion normal saline until vital signs have improved.
When the plasma glucose reaches the range 11 to 13 mmoll/l, 5 % glucose should be added to
the intravenous fluids to avoid the risk of hypoglycemia. Following recovery the acute episode,
patients are usually switched to adjusted doses of subcutaneous regular insulin at 4 to 6-hour
intervals. When they are able to eat, this is changed to a 1 or 2 injection regimen.
Treatment of electrolyte disorders.
Once urine flow has been reestablished, potassium should be added to begin repletion of the
total body deficits.
Potassium replacement is usually started by adding 20 mmoll/l to the initial liter of the
intravenously-infused 0,45 % sodium chloride with careful serum potassium and ECG monitoring.
Lactic acidosis (LA).
DM is one of the major causes of LA, a serious condition characterized by excessive
accumulation of lactic acid and metabolic acidosis.
Pyruvic acid
Lactic acid
NADH
NAD
Acetoacetic
Beta-hydroxybutyric
The hallmark of LA is the presence of tissue hypoxemia, which leads to enhanced anaerobic
glycolysis and to increased lactic acid formation.
Piruvic acid is converted into lactic acid by lactic dehydrogenase (LDH) in the presence of
reduced nicotinamide adenine dinucleotide (NADH), which, in turn, is converted into NAD. The
reaction is reversible and involves LDH in both directions. The conversion of acetoacetic acid into
beta-hydroxybutyric acid also requires the oxydation of NADH. LA results from decreased
availability of NAD caused by lack of oxygen. Likewise, the deficiency of NAD impairs the
conversion of beta-hydroxybutyric into acetoacetic acid. Thus, LA predisposes to accumulation of
beta-hydroxybutyric acid, which does not react with acetest tablet, so, the reaction for ketone bodies
may be negative or slightly positive. The normal blood lactic acid concentration is 1mmol/l, and the
pyruvic to lactic ratio is 10:1. An increase in lactic acid without concomitant rise in pyruvate leads
to LA of clinical importance.
Predisposing factors.
1.
2.
3.
4.
Heart and pulmonary failure (which leads to hypoxia).
Usage of bigyanids, pheformin therapy.
Alcohol intoxication.
Ketoacidosis (it is important to have a very high index of suspection with respect to presence of
LA).
Clinical presentation.
Signs and symptoms.
1. Kussmaul breathing (deep, sighing respiration) is present as respiratory compensation for the
metabolic acidosis and is obvious when the pH is less than 7.2.
2. Symptoms of central-nervous-system involvement include headaches, drowsiness, lassitude.
3. Anorexia, nausea, vomiting, and abdominal pain may be present.
4. Myalgia is common.
Physical examination.
1. Acrocyanosis is common.
2. Tachycardia frequently is present, blood pressure is decreased.
3. Poor skin tugor and dry skin may be prominent.
4. Hypothermia is common in LA.
5. Hyperpnea or Kussmaul respiration are present and related to degree of acidosis.
4. Findings associated with coexisting medical problems (e.g., renal disease, cardiovascular
disease) may be evident.
Laboratory findings.
1. Blood glucose level is not high
2. Glucosurea is absent.
3. Blood lactic acid is high.
Treatment.
LA is treated by correcting the underlying cause.
In severe cases, bicarbonate therapy should be used (intravenously-infused 2,5 % sodium
bicarbonates 1 to 2 l/day).
LA can be treated with low dose insulin regimens with 5 % glucose solution infusion.
Volume expanders and oxygen therapy are helpful treatment as well.
Comparison of DCA, HNC and LA.
DKA
HNC
LA
Age
Below 40
Above 40
Above 40
Type of DM
Type I
Type II
Type II
Predisposing factor Insulin deficiency
Dehydration
Hypoxia
Prodromes
Several
days Several
days Less than 1 day
duration or less duration
than 1 day
Underlying renal, About 15 %
About 85 %
About 90 %
cardiovascular or
pulmonary disease
General
More acidic and More dehydrated More acidic and
less
dehydrated, and less acidic, no less
dehydrated,
hyperventilation
hyperventilation
hyperventilation
Neurologic
Rare
Very common
Very common
symptoms
and
signs
Laboratory findings
- blood glucose
High (about 20 – Very high (about Normal or about 10
30 mmoll/l)
40 – 50 mmoll/l)
– 11 mmoll/l
- plasma ketones
+
- serum sodium
Normal, elevated or Normal, elevated or Normal
low
low
- serum potassium
Normal, elevated or Normal, elevated or Normal
low
low
- serum bicarbonate Low
Normal
Low
- blood pH
Less than 7,35
Normal
Less than 7,35
- serum osmolality Less than 330 Over 350 mOsm/l
Normal
mOsm/l
- free fatty acids
or normal
Normal
Complications:
- Thrombosis
Rare
Frequent
Very rare
- Mortality
1 – 10 %
20 – 50 %
About 90 %
Diabetes treatment Always insulin
Diet alone or oral Diet alone or oral
after recovery
agents, sometimes agents, sometimes
insulin
insulin
Hypoglycemia
It is a syndrome characterized by symptoms of sympathetic nervous system stimulation or
central nervous system dysfunction that are provoked by an abnormally low plasma glucose level.
Hypoglycemia represents insulin excess and it can occur at any time.
CAUSAL FACTORS OF HYPOGLYCEMIA IN DIABETIC PATIENTS
A. Problems with insulin
I. Management errors
- patient error
- physician error
- pharmacy error
- drug interaction
- other related conditions
(endocrine failure: Addison’s disease, Hypopituitarism, hypothyroidism)
II
Altered
pharmacokinetics
of
insulin
– change of insulin species
– change of formulation
– excessive dose
– injection: site, size, depth
– absorption: muscle exercise, massage, temperature
– delayed clearance: insulin antibodies, renal failure, hepatic failure
III. Sensitivity
to
insulin
–
insulin
antibodies
– exercise
– weight reduction
– diurnal variation
– diabetic pregnancy and following delivery
– menstrual cycle
– acute remission following treatment of type 1 diabetes
– alcohol
B. Inadequate carbohydrate – missed or delayed meals – excessive /
unpremeditated exercise – delayed gastric emptying (autonomic
neuropathy)
– malabsorption (coeliac disease, pancreatic exocrine failure) – slimming diets
(anorexia nervosa) – pregnancy: breastfeeding
Precipitating factors.
irregular ingestion of food;
extreme activity;
alcohol ingestion;
drug interaction;
liver or renal disease;
hypopituitarism and adrenal insufficiency.
Clinical presentation.
Signs and symptoms.
Two distinct patterns are distinguished:
1) adrenergic symptoms (they are attributed to increased sympathetic activity and epinephrine
release): sweating, nervousness, tremulousness, faintness, palpitation, and sometimes hunger;
2) cerebral nervous system manifestations: confusion, inappropriate behavior (which can be
mistaken for inebriation); visual disturbances, stupor, coma or seizures. (Improvement in the
cerebral nervous system manifestations will be with a rise in blood glucose.)
A common symptom of hypoglycemia is the early morning headache, which is usually
present when the patient awakes.
Patients should be familiar with the symptoms of the hypoglycemia but some of them are not
heralded by symptoms.
Physical examination.
1. The skin is cold, moist.
2. Hyperreflexia can be elicited.
3. Hypoglycemic coma is commonly associated with abnormally low body temperature
4. Patient may be unconsciousness.
Laboratory findings.
1. Low level of blood glucose
-
Common symptoms of hypoglycemia in different age groups
Children
Elderly
Young adults
Tremor
Hunger
Pallor
Tremor
Hunger
Pounding heart
Sweating
Tremor
Drowsiness
Poor concentration
Drowsiness
Odd behaviour
Confusion
Incoordination
Speech diffculty
Nonspecifc
Nausea
Headache
Drowsiness
Poor concentration
Confusion
Weakness
Dizziness
Neurological
Unsteadiness
Poor concentration
Double vision
Blurred vision
Slurred speech
Weakness
Dizziness
Behavioral
Tearful
Confusion
Tiredness
Irritable
Aggressive
Pounding heart
Sweating
Anxiety
Treatment.
Insulin–treated patients are advised to carry sugar lumps, candy, or glucose tablets at all
time.
If the symptoms of hypoglycemia develop, the patients have to drink a glass of fruit juice or
water with 3 tbsp. of table sugar added or to eat candy, and to teach their family members to give
such treatment if they suddenly exhibit confusion or inappropriate behavior:
1) glucagon 0,5 – 1 unit (0,5 – 1 ml) s/c, i/m or i/v. If the patient does not respond to 1 unit of
glucagon within 25 minutes, further injections are unlikely to be effective, and are not
recommended;
2) an i/v injection of 20 or 100 ml of 40 % glucose, followed by a continuous infusion of 5 %
glucose (10 % glucose may be needed) until it clearly can be stopped safely;
3) glucocorticoids and adrenaline are helpful as well.
Clinical
features
Age
Eye tone
Dehydratation
Acetone
breath,
acetonuria
hyperglycemia
glucosuria
Blood pressure
Brain edema
Blood
osmolality
Muscle tone
pH of blood
hypoglyce
mic age
Any
N
N
N
↑
N
Differentiate diagnosis of diabetic comas
Coma
ketoacidotic hyperosmolar Lactic acidosis
Often less Often more Often more than
than 40 y.
than 40 y.
40 y.
↓
↓
N
+
++
+
++
++
↓
↑
N, ↓
↓
++++
++
↓
+/↑
N, ↓
N
+/+/↓
N
N
↓
Note: “-” - symptom absent, “+” - symptom present, ↑ - elevation, ↓ - decrease, N - norm.
Tests and Assignments for Self-assessment.
Multiple Choice.
Choose the correct answer/statement:
1. A patient has been diagnosed with lactic acidosis. This condition is caused by:
A. insulin deficiency
B. dehydration
C. extreme activity
D. hypoxia
E. intercurrent infection
2. A patient with DKA has deep signing respiration. Kussmaul breathing is caused by:
A. hyperglycemia
B. metabolic acidosis
C. dehydration
D. hypokalemia
E. ketonemia
3. The patient of 63 years suffers from insulindependent form of diabetes. On the background of
acute infringement of the cerebral circulation the high hyperglycemia - 56 mmol/l, severe
dehydration, hyper-chloremia, hypernatremia has developed. The ketonemia and acetonuria are
absent. Establish the correct diagnosis:
A. Hyperosmolar coma
B. Acute renal failure
C. Diabetic hyperketonemic coma
D. Chronic renal failure
E. Hyperlactacidemic coma
4. Patient С., 24 years with the 10-years experience of diabetes type 1 is unconsciousness, the skin
is wet. Respiration is superfcial, the arterial pressure - 140/70 mmHg. Tone of muscles and tendon
refexes are raised. Establish the diagnosis:
A. Hypoglycemic coma
B. Lactoacidotic coma
C. Hyperosmolar coma
D. Diabetic ketoacidotic coma
E. Cerebral coma
Answer: 1 – D. 2 – B. 3 – A. 4 – A.
Real-life situations to be solved:
Patient D., 35 years, was hospitalized. She is unconscious. Her relatives told you, that she has
type I DM and felt herself bad 3 days ago after diarrhea, when she decreased the dose of insulin.
She had weakness, fatigue, nausea and vomiting. Examination: patient is unconscious, dry skin and
tongue, hyporeflexia. Laboratory findings: blood glucose level – 28 mmoll/l, acetone in urine –
positive. What is your previous diagnosis?
Answer: Ketoacidotic coma.
Patient F., 27 years, complains on regular morning headache, which is present when he awakes.
Patient has type I DM and takes 82 units of insulin/day. What is your previous diagnosis?
Answer: Hypoglycemic status. (You have to investigate blood glucose level at 3 o’clock in the
morning and if the level is low decrease the dose of insulin.)
Students Practical Activities.
Work 1 : Students’ group is divided into 2 sub-groups, that work near the patients’ bed: ask the
patients on organs and systems, take anamnesis of the disease , anamnesis of life, make objective
exam. With the teacher’s presence. In the class-room they discuss the patients, learn data of
laboratory and instrumental exam. of these patients.
1.To group the symptoms into the syndromes.
2.To find out the leading syndrome and make differential diagnosis.
3.To formulate the diagnosis.
4.To make a plan of treatment.
Methodological recommendation prepared assistant, c.m.s. Chernobrova O.I.
It is discussed and confirm on endocrinology department meeting
" 31 " august 2012 y. Protocol № 1.