Universidad La Salle

Mexico’s Medical Faculty

University Extension Course for the National Exam Preparation
For the Medicine Residency Aspirers
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Clinical Case 20c

A 20 year old male who is sent to the emergency room brought in by his family, who has had
diabetes mellitus since he as 13 years old who was given an irregular treatment with a diet and
intermediate-acting insulin. His relatives mentioned that in recent days he had shown fatigue,
weakness, anorexia, nausea and some vomiting (gastrobiliar content, polyuria, diffuse abdominal
pain located in mesogastrio gnawing.) In the last two days the patient had been drinking alcohol
and suspended his insulin injections. The patient on arrival to the hospital entry had an stuporous
state which is clearly evident.

1.- With this clinical data it is very probable that among any lab studies elaborated on the patient
there would be found:

a) Normal Plasmatic Osmolarity.

b) Leucopaenia
c) Hypoglouconemia
d) Hyponatraenia

Concept:
Hyponatremia is the plasma concentration of Na + <135 mEq / l. The symptoms of
hyponatremia causes hyperhydration resulting from neuronal due to the passage of water
inside the cells, secondary to hypoosmolality in the extracellular space.

Seriousness of these Symptoms:

Confusion
Anorexia
Lethargy, stupor or coma
Vomiting
Seizures
It will depend on the onset speed of hyponatremia and its intensity

CLINICAL
Clinical manifestations of hyponatremia are related to osmotic water movement leading to
increased intracellular fluid volume, particularly at the neuronal level, triggering cerebral edema.
Symptoms and severity depend on the rapidity of onset and the decrease in plasma concentration
of Na +. As the lower the concentration, which you will observe:

Nausea, vomiting
Muscle manifestations (weakness, cramps, ileus)
As it descends the concentration of Na + in plasma, symptoms will worsen, in which the following
will appear:

Headache
Lethargy
Confusion
Drowsiness
Only if the plasma Na concentrations are <110 mmol / L or drop suddenly, it will be found:

Seizures
Coma
In chronic hyponatremia are compensatory mechanisms that achieve the loss of Na + and K + and
organic osmolytes by brain cells onto secondary movement of water through the cells (from
intracellular to extracellular fluid). The final consequence is that it will decrease cerebral edema
and its symptoms.

Diagnostic algorithm:
 Diagnostic algorithm for hyponatremia

Bibliography:

• Rose BD, Post TW. Hyponatremia hypo-osmolarity-situations. In: Rose BD, Post
TW, eds. Electrolyte disorders and acid-base, Marban SL Books, 2001, 697-745

• JC Ayús. Disorders of body fluids osmolarity: changes of sodium. In: L. Hernando

eds. Clinical Nephrology, 2nd ed, Panamericana, 2003, 46-55

• Berl T, J. Verbal Pathophysiology of Water Metabolism. In: Brenner BM, eds The
Kidney, 7th edition, Saunders, 2002, 857-919
 • 2 .- It is more likely that the clinical framework corresponds to:

a)Lactic acidosis type B.

b)Alcoholic ketoacidosis.
c) Hypoglycemia and acute alcoholism.
d)Diabetic ketoacidosis.

• DEFINITION

While Lebovitz in his 1995 review mentioned that there is no consensus definition, we can
consider that the definition published in 1996 by the American Diabetes Association for
Hospital Admissions in diabetic patients. One patient had an episode of CAD when:
• The blood glucose is above 250 mg / dl (> 14 mM / l)
The arterial pH is less than 7.35, venous pH is less than 7.30 or serum bicarbonate less
than 15 mEq / l.
There is the presence of ketonuria and / or ketonemia.
• Diabetic ketoacidosis (DKA) is one of the most serious acute metabolic complications of
diabetes mellitus caused by a relative or absolute deficiency of insulin and a concomitant
increase of contra insulars hormones. It is characterized by a marked catabolic disturbance
in the metabolism of carbohydrates, proteins and lipids, classically presenting with the
triad of hyperglycemia, ketosis and acidosis.

PATHOPHYSIOLOGY
HORMONE ACTION ON INTERMEDIATE METABOLISM

The CAD is caused primarily by an absolute or relative deficiency of insulin, a hypoglycemic

hormone. In the regulation of blood sugar hormones are involved a group of anti-hyperglycemic or
regulatory action, that can be fast (adrenaline and glucagon) or slower (somatotropin,
glucocorticoids, prolactin and thyroxine), whose increase has a role in the pathophysiology of DKA
and nonketotic hyperosmolar state (EHNC), which some authors regard as the result of a
pathophysiological state of common5 DKA. It will predominate in insulin deficiency and EHNC,
increased on back-regulator hormones.

Among many functions of insulin, it emphasizes the role of promoting entry of glucose into target
tissues by stimulating the conveyor. This feature allows classification of tissue in:

• Insulin Sensitive: cannot use glucose for energy in the absence of insulin, such as liver, muscle
and adipose tissue, among others.
• Insulin Insensitive: can use glucose for energy in the absence of insulin, such as brain tissue and
erythrocytes.

Insulinosensible tissues are where important metabolic changes occur due to insulin deficiency.
Although they are closely related considerations we will separate the intermediate metabolism in:

• Changes in the metabolism of carbohydrates

Typical hyperglycemia of CAD is mainly due to two main mechanisms:

1. In all insulinosensible tissues there is a decrease in the entry and subsequent utilization of
glucose and
2. In the liver area, an increase mainly glycogenolysis and gluconeogenesis, thus increasing the
level of circulating glucose.

• Alterations in lipid metabolism and source of ketone bodies.

Increased counter-regulatory hormones play here a more prominent role in addition to the insulin
deficiency. There was an increase of lipolysis leading to increased of free fatty acids. These fatty
acids are metabolized by the β-oxidation incomplete as the Krebs cycle is blocked and generate
ketone bodies in the mitochondria of hepatocytes. This mechanism called Ketogenesis gives rise to
acetoacetic acid and β-Hydroxybutyric and Acetone. Thus this also decreased peripheral utilization
of ketone bodies, which is why maintaining and increasing its circulating level.

• Alterations in protein metabolism

Proteolysis is increased originating amino acids in the liver, used as precursors in gluconeogenesis.

• Interrogation and physical examination

Although the symptoms of poorly controlled diabetes mellitus may be present from several days
earlier, the metabolic alterations typical of CAD usually develops quickly (usually within 24 hours.)

The clinical picture includes a history of polyuria, polydipsia, weight loss, nausea, vomiting and
decreased appetite. This relative anorexia is critical because it is the first manifestation of the
transition from simple hyperglycemia to ketosis. Occasionally, it appears in the adult abdominal
pain (more common in children), which can simulate an acute surgical abdomen; the cause of this
pain is not fully elucidated and is attributed to dehydration of muscle tissue, gastric dilatation and
paralytic ileus (secondary to electrolyte disturbance and metabolic acidosis). Another theory
relates it to changes in PG.
The metabolic diagnosis of acute abdomen can only be accepted when there’s no other
reasonable cause of abdominal pain, the pH is low and the symptoms improve with any correction
of acidosis; therefore, if there is no improvement in less pain, it should exclude other diagnostic
possibilities such as mesenteric thrombosis and acute pancreatitis (secondary to severe
hypertriglyceridemia may accompany CAD).

The altered state of consciousness, mainly lethargy and sleepiness, are often of delayed onset and
may progress to coma in untreated patients. A small number of cases result in coma. Other
symptoms include overall weakness, fatigue and getting tired more easily.

3 .- A physiological phenomenon that often occurs in these cases is:

a) Increased production of pyruvate.

b) Excess of glucagon in plasma.
c) Decreased liver fatty acids.
d) Removal of the action of carnitine acyltransferase.
GLUCAGON
Glucagon release is stimulated when insulin is unable to provide the cells needed glucose for
energy. Glucagon increases the amount of glucose in the bloodstream by the catabolism of stored
glucose (glycogenolysis) and the conversion of carbohydrate molecules to glucose
(gluconeogenesis). The blood glucose concentrations in patients with CAD typically range between
300 and 800mg/dl blood. The CAD cannot be diagnosed only in terms of blood glucose
concentrations, as the ketoacidosis is also a factor.
Bibliography

1. Wagner A, Risse A, Brill HL et at. Therapy of Severe diabetic ketoacidosis. Diabetes Care
1999,22:674 – 677.
2. Delaney MF, Zisman A, Kettyle WM. Diabetic ketoacidosis and hyperosmolar nonketotic syndrome.
Endocrinol Metab Clin North Am 2000; 29(4): 683–705
3. Kitabchi AE, Wall BM. Management of diabetic ketoacidosis. Am Fam Physic 1999; 60: 455 –464.
4. Umpierrel GE, Khajavi M, Kitabchi AE. Review: Diabetic ketoacidosis and hyperglycemic
hyperosmolar nonketotic syndrome. Am J Med Sci 1996; 311:225–233
5. Kitabchi AE, Wall BM. Diabetic ketoacidosis. Med Clin North Am 1995; 79(1): 9–37
6. Rucker DW. Diabetic ketoacidosis. Medicine Journal 2001; 2(4)
7. American Diabetes Association. Hyperglycemic crises in patients with diabetes mellitus. Diabetes
Care 2001; 24 (Suppl 1): S83– S90
8. Magee MF, Bhatt BA. Management of descompensated diabetes. Diabetic ketoacidosis and
hyperglycemic hyperosmolar syndrome. Critical Care Clinics 2001; 17(1): 75–106
9. Kitabchi AE, Umpierrel GE, Murphy MB, Barrett EJ, Kreisberg RA, Malone JI, Wall BM. Management
of hyperglycemic crises in patients with diabetes (technical review). Diabetes Care 2001; 24(1):
131–153
10. Garber AJ. Diabetes Mellitus. In: Stein JH (Editor in Chief). Internal Medicine. Fourth Edition. Mosby;
1994,1391–1424

4 - In relationship to the pathogenesis of insulin-dependent diabetes, this is a process:

a) Purely genetic.
b) Depending on its environment.
c) Abnormal insulin secretion.
d) Resistance to insulin action.

Diabetes mellitus type I or also known as juvenile diabetes or insulin dependent diabetes mellitus
is a metabolic disorder characterized by selective destruction of pancreatic β cells causing absolute
insulin deficiency. It differs from type 2 diabetes mellitus because it is a type of diabetes
characterized by early age occurs in life, usually before age 30. Only 1 in 20 people with diabetes
have type I diabetes, which occurs most often in young children. The administration of insulin in
these patients is essential. Type 1 diabetes is classified as autoimmune cases, the most common
form, and idiopathic cases. . Type 1 diabetes mellitus is a chronic autoimmune disease whose
primary pathophysiologic event is based on a "insulinitas", which is characterized by an
inflammatory infiltrate of inflammatory pancreatic acini with a predominance of CD8 T
lymphocytes and a variable number of CD4. The destruction is selective towards cells, resulting
in cell death 80% of these cells to the onset of symptoms. Their chronic sequelae because of
microangiopathy and neuropathy produce high morbidity and mortality in patients who have it.

Jean-Louis Chiasson, Diagnosis and treatment of diabetic ketoacidosis; and the hyperglycemic hyperosmolar
state; CMAJ 2003;168(7):859-66.

Todd, J.A., Bell, J.I. & McDevitt, H.O. HLA-DQ beta gene contribuyes to susceptibility and resistance to insulin
dependent diabetes mellitus. Nature 1987; 329:599-604.

2. Mc Devitt, H.O. & Tyan, M.L. Genetic control of the antibody response in inbred mice.

Transfer to response by spleen cells and linkage to the mayor histocompatibility (H-2)

locus. J Exp Med 1968; 128(1): 1-11.

3. Insulinodependient Diabetes Mellitus. ILADIBA. January 1995 : 14-8.

4. Frazer de Llado, T.E., González de Pijem & Hawk, B. Incident of IDDM in children living in Puerto Rico.
Puerto Rico IDDM Coalition. Diabetes Care 1998; 21(5): 744-6.

5. Carrasco, E., Pérez, F., Calvillan, M., López, G., Wolf, C., Castano, A. & García de los Ríos,

M. Incident of insulin-dependent diabetes mellitus in Santiago, Chile (1990-1993).

Revista Médica de Chile 1996; 124(5): 561-6.

6. Ferreira, S.R., Franco, L.J., Vivolo, M.A., Negrato, C.A., Simoes, A.C. & Ventureli, C.R. Population-based
incident of IDDM in The State of Sao Paulo, Brazil. Diabetes Care 1993; 16(5): 701-4.

7. Bach, J.F. Predictive medicine in autoimmune diseases: from the identification of genetic predisposition
and environmental influence to precocious immunotherapy. Clin Immunol, Immunopathol 1994;72:156-161

5 .- The following clinical data is very characteristic of this disease:

a) Kussmaul breathing.
b) Absence of brainstem reflexes.
c) Sign of Babinski.
d) Tetany.
Physical examination showed signs of
dehydration (loss of skin turgor, dry
mucous membranes, tachycardia and
hypotension) that lead to a hypovolemic
shock. You can see a typical breathing
pattern (Kussmaul breathing) with deep
breathing, slow regular and perceived
an odor characteristic, bad
apples in the exhaled air. .Kussmaul
breathing appears when the pH is less
than 7.20 to 7.10, so is the clinical signs
appear when the patient has gone from
a state of ketosis to one of ketoacidosis.
When the pH is very low (£ 6.9) may
disappear due to involvement of bulbar center, which is a sign of poor prognosis.

Jean-Louis Chiasson, Diagnosis and treatment of diabetic ketoacidosis; and the hyperglycemic hyperosmolar
state;CMAJ 2003;168(7):859-66.

6 .- The most likely cause of cardiac arrest in this patient during the first hours of hospitalization
would be:

a) Hyperkalemia.
b) Iatrogenic hypoglycemia.
c) Persistent metabolic acidosis.
d) Cerebral edema.

Serum potassium concentrations are high due to the movement of intracellular potassium into the
extracellular space caused by acidemia, hypertonicity and insulin deficiency. It should be closely monitored
for treatment-value for it drops rapidly (initial levels <4.5 mmol / L indicating a strong depletion and the
need for prompt treatment and close cardiovascular monitoring and treatment can decrease even more and
cause cardiac abnormalities. The serum concentrations decrease as a result of insulin therapy, correction of
acidosis and volume expansion. That is why the development of severe hypokalemia is the most serious
electrolyte disorder that occurs during treatment. To prevent losses must be replaced with a target serum
concentration between 4 and 5 mmol / L.
Electrocardiogram is important to monitor blood levels of potassium.

Hyperkalaemia:
Peaked T waves (QT interval normal or slightly reduced)
PR interval prolongation with ST depression
Progressive disappearance of the P wave
Progressive heart block
Ventricular arrhythmias
Cardiac arrest

Peaked T waves are the ECG data in the most consistent in hyperkalemia.

REFERENCES

- Brenner, BM, Rector FC, eds. The Kidney. W B Saunders, Philadelphia, 1991.
- Massry, SG, Glassock, RJ, eds. Textbook of nephrology. 3rd ed. Williams &
Wilkins, Baltimore, 1995.
- Narins, RG, ed. Clinical Disorders of fluid and electrolyte metabolism. 5th ed.
McGraw - Hill, New York, 1994.
- "Washington Manual of medical therapeutics. " 9th. edition. Ed Masson
- "Principles of Internal Medicine Harrison. " 13th. edition. Inter-
McGraw-Hill

7 .- The initial treatment for this condition is:

a) Measure plasma lactate and pyruvate.

b) General measures and liquid i.v.
c) Measuring serum and urine osmolarity.
d) To administer insulin and to determine anion gap.
8 .- After the administration of insulin and monitoring blood glucose levels every time it detects
that no figures have been reached between 50 and 70 mg / dl, then you will decide to:

a) Increase the amount of fluid

b) Doubling the dose or giving bowling i.v. (10u.)
c) Wait 12 hours to obtain goals
d) Administer bolus of 0.5 U.

9 .- When we appreciate glucose levels below 250 mg / dl, normal Na and mild hypotension, we
decided to continue with the next solution parenterally

a) Hartman 1000 ml / 4 hrs

b) 5% glucose saline (0.45%) to 150 or 250 mL / h
c) Continue with physiological sol 1000ml / hr.
d) Mixed Sol 1000ml / 8 hrs

Answers to questions 7, 8 and 9.

Bibliography:

1. Wagner A, Risse A, Brill HL et al. Therapy of severe diabetic ketoacidosis. Diabetes Care
1999,22:674 – 677,

2. Delaney MF, Zisman A, Kettyle WM. Diabetic ketoacidosis and hyperosmolar nonketotic
syndrome. Endocrinol Metab Clin North Am 2000; 29(4): 683–705

3. Kitabchi AE, Wall BM. Management of diabetic ketoacidosis. Am Fam Physic 1999; 60: 455
–464

4. Umpierrel GE, Khajavi M, Kitabchi AE. Review: Diabetic ketoacidosis and hyperglycemic
hyperosmolar nonketotic syndrome. Am J Med Sci 1996; 311:225–233

5. Kitabchi AE, Wall BM. Diabetic ketoacidosis. Med Clin North Am 1995; 79(1): 9–37

6. Rucker DW. Diabetic ketoacidosis. Medicine Journal 2001; 2(4)

7. American Diabetes Association. Hyperglycemic crises in patients with diabetes mellitus.

Diabetes Care 2001; 24 (Suppl 1): S83– S90

8. Magee MF, Bhatt BA. Management of descompensated diabetes. Diabetic ketoacidosis

and hyperglycemic hyperosmolar syndrome. Critical Care Clinics 2001; 17(1): 75–106-