ACID BASE BALANCE,

ENDOCRINE DISORDERS
(Hypercalcemia, Hypocalcemia,
Hyperkalemia, Hypokalemia,
DM)
By-Sangeeta Dutta
INTRODUCTION

Acid-base balance is very important for the homeostasis of the body and
almost all the physiological activities depend upon the acid-base status of
the body. Acids are constantly produced in the body. Acid production is
balanced by the production of bases so that the acid-base status of the
body is maintained.

An acid is the proton donor (the substance that liberates hydrogen ion). A
base is the proton acceptor (the substance that accepts hydrogen ion)
REGULATION OF ACID-BASE
BALANCE
Body is under constant threat of acidosis because of the production of
large amount of acids. Generally, two types of acids are produced in the
body:
1. Volatile acids
2. Non-volatile acids.
Cont..
1. Volatile Acids: Volatile acids are derived from CO2. Large quantity of
CO2is produced during the metabolism of carbohydrates and lipids.
This CO2 is not a threat because it is almost totally removed through
expired air by lungs.
2. Non-volatile acids are produced during the metabolism of other
nutritive substances such as proteins. These acids are real threat to the
acid-base status of the body.
ENDOCRINE DISORDERS
 CALCIUM
Our body takes calcium by ingested food. Mostly (99%) calcium is
located in the skeletal system.
Parathyroid Hormone (PTH) controls the calcium imbalance by
parathyroid gland.
Clcitonin is produced by c-cells of thyroid gland and stimulated by
high serum levels of calcium.
Calcium is absorbed in the presesence of Vitamin D and gatric cidity
and excreted in the faeces.
The normal serum calcium level is 8.6- 10.2 mg/dl. (2.2 - 2.6 mmol/L).
HYPERCALCEMIA
DEFINITION
Hypercalcemia is a corrected total serum calcium value above the upper
limit of the normal range or an elevated ionized calcium value.
CLASSIFICATION

According to level of corrected total serum calcium value

hypercalcemia can be classified into:

Mild Hypercalcemia (Ca level >10.5 mg/dL to less than 12 mg/dL)

Moderate Hypercalcemia (Corrected Ca Level 12 to 14 mg/dL)

Severe Hypercalcemia (A level greater than 14 mg/dL)

CLINICAL FEATURES
Hypercalcemia can be completely asymptomatic.
Central nervous system effects: Lethargy, depression, psychosis, ataxia, stupor,
and coma
Neuromuscular effects: Weakness, proximal myopathy, and hypertonia
Cardiovascular effects: Hypertension, bradycardia (and eventually asystole), a
shortened QT interval (ECG).
Renal effects: Stones, decreased GFR, polyuria, nephrocalcinosis;
Gastrointestinal effects: Nausea, vomiting, constipation and anorexia
Eye findings such as band keratopathy Systemic metastatic calcification.
CAUSES
PRIMARY HYPERPARATHYROIDISM:
Primary hyperparathyroidism results from the excessive secretion of
PTH.
Primary hyperparathyroidism is approximately 2 to 3 times more
common in women than in men.
The diagnosis of primary hyperparathyroidism in a hypercalcemic
patient can be made by determining intact PTH level.The definitive
treatment of primary hyperparathyroidism is parathyroidectomy.
Cont...
MALIGNANCY-ASSOCIATED HYPERCALCEMIA:
Malignancy- associated hypercalcemia is the second most common
form of hypercalcemia.
It can be presented as a part of paraneoplastic syndrome (eg:
parathyroid hormone (PTH)-related protein (PTHrP)) or due to direct
bony metastasis.
It is most common in squamous cell carcinoma of the lung, head, and
neck, renal cell carcinoma, breast cancer, multiple myeloma, and
lymphoma.
Cont...
Others causes:-

Calcium & Vitamin D (Hypervitaminosis –D) over Supplimentation

Sarcoidosis and Other granulomatous disorders

Endocrinopathies: Thyrotoxicosis, Adrenal Insufficiency.

Milk Alkali Syndrome: Ingesting large amounts of calcium containing

antacids.
PATHOPHYSIOLOGY
Excessive secretion of calcium

Increase bone reabsorption

Increase GI absorption of calcium

Decrease renal excretion of sodium

Hypercalcemia
DAILY REQUIREMENT OF CALCIUM
1 to 3 years = 500 mg
4 to 8 years = 800 mg
9 to 18 years = 1,300 mg
19 to 50 years = 1,000 mg
51 years and above = 1,200 mg
Pregnant ladies and lactating mothers = 1,300 mg
DIAGNOSIS/ INVESTIGATIONS
General Investigations are-

Serum Calcium Level: Serum calcium is a blood test to measure the amount of
calcium in the blood. Serum calcium is usually measured to screen for or
monitor bone diseases or calcium-regulation disorders (diseases of the
parathyroid gland or kidneys)

Serum Alkaline phosphates: Serum calcium, phosphate, and alkaline phosphatase

were measured using the ARCHITECT C8000 autoanalyzer.
Cont...
Serum Parathyroid level: PTH is an important regulator of calcium and phosphate
homeostasis and bone remodeling. Its measurement is important for different
purposes.
The first is the diagnostic workup of hypocalcemia and hypercalcemia. In patients
with hypercalcemia, PTH differentiates between hyperparathyroidism, in which
PTH is abnormally high compared with what would be expected with regard to the
calcium concentration, and other causes of hypercalcemia, in which PTH is low. The
second is the analysis of secondary hyperparathyroidism (SHPT), in which PTH
concentrations are elevated because of hypocalcemia, hyperphosphatemia, or
vitamin D deficiency. SHPT may develop in patients with chronic kidney disease
(CKD) and in patients who have undergone bariatric surgery. These patients are
likely to develop various degrees of metabolic bone disease (MBD).
Cont...
Serum Vitamin-D level: Excessive amount of vitamin D in the body can
cause too much calcium to circulate in the blood, which can lead to
confusion, loss of appetite, vomiting, and muscle weakness.
Other investigation like-
Serum Total protein
Serum Albumin
ECG
Specific Investigations: Varies according to cause.
TREATMENT
• Patients with asymptomatic or mildly symptomatic ( hypercalcemia do
not require immediate treatment.
• Similarly, a serum calcium of 12 to 14 mg/dL may be well tolerated
chronically and may not require immediate treatment.
• However, an acute rise to these concentrations may cause marked
changes in sensorium, which requires more aggressive measures. In
addition, patients with a serum calcium concentration >14 mg/dL (3.5
mmol/L) require treatment, regardless of symptoms.
Cont...
• Patients with mild hypercalcemia with asymptomatic or mildly
symptomatic hypercalcemia do not require immediate treatment.
• However, they should be advised to avoid factors that can aggravate
hypercalcemia, including thiazide diuretics, volume depletion,
prolonged bed rest or inactivity, and a high calcium diet.
• Adequate hydration (at least six to eight glasses of water per day) is
recommended to minimize the risk of nephrolithiasis.
• Additional therapy depends mostly upon the cause of the
hypercalcemia.
Cont...
Patients with moderate hypercalcemia may not require immediate
therapy.
It is important to note that an acute rise to these concentrations may
cause marked changes in sensorium, which requires more aggressive
therapy.
In these patients, treatment with saline hydration and bisphosphonates,
Cont...
Patients with severe hypercalcemia require more aggressive therapy.
Volume expansion with isotonic saline at an initial rate of 200 to 300
mL/hour that is then adjusted to maintain the urine output at 100 to 150
mL/hour.
In the absence of renal failure or heart failure, loop diuretic therapy to
directly increase calcium excretion is not recommended, because of
potential complications.
Administration of salmon calcitonin (4 IU/kg) and repeat measurement
of serum calcium in several hours. It can be repeated every 6 to 12 hours
(4 to 8 IU/kg).
The concurrent administration of zoledronic acid (ZA; 4 mg
intravenously [IV] over 15 minutes) or pamidronate (60 to 90 mg over
two hours), preferably ZA because it is superior to pamidronate in
reversing hypercalcemia related to malignancy.
HYPOCALCEMIA
Occurs when ionized calcium in serum falls below 1.16 mmol/L
(3.4.4mg/dl).
CAUSES
• Hypoparathyroidsim
• Autoimmune diseases
• Hypoalbuminemia
• Defect in Vit D metabolism
• Malabsorptions
• Drugs
• Renal and liver diseases
SIGN AND SYPTOMS
Fatigue
Muscle cramps
Tetany
Seizure
Chvostek’s sign
Trousseau’s sign
Irritability, Psychosis, Depression
ECG abnormalities
Chvostek’s sign
Trousseau’s sign
DEFINITION
Hypokalemia is serum potassium level of less than 3.5mEq/L, it is
common electrolyte disorder.
CAUSES
Gastrointestinal losses:-Vomitting, diarrhea, nasogastric suctioning,
intestinal fistula, laxative abuse, excessive tap water, enemas.
Dietary changes:- Malnutrition, starvation, potassium free diet, some
weight reduction.
Medications:- Potassium wasting diuretics (thiazide, loop of Henle
and osmotic steroids, cortisone preperations), large amounts of licorice
(aldosterone like effect), gentamycin, amphoterecin B, digitalis
preperations and beta adrenergic promote potassium loss.
Cont...

Redistribution of potassium:- Insulin movesback into cells, potassium

loss from osmotic diuresis, in diabetic acidosis, alkalosis causes
potassium to shift into cells in exchange for hydrogen ion.

Disorders:- Cushing’s syndrome, diuretic phase of acute renal failure,

alcoholism, hyperaldosteronism.
SIGN & SYMPTOMS
GI: Anorexia, vomitting, diarrhea, ileus distension.
Musculoskeletal:- Muscle weakness, paralysis, leg cramps, muscle flabbiness.
Cardiovascular:- Dysrrhythmia, vertigo, flattenedT wave, prominent U wave,
slow weak pulse.
Respiratory:- Shallow respirations, shortness of breathe.
Neurologic:- Fatigue, lethargy, decreased tendon reflexes, confusion,
depression. Renal:- Polyuria, decreased reum osmolality, nocturia.
Pathophysiologic basis:- - Smooth muscle contraction slowed. - Slowed
smooth muscle and skeletal muscle contraction. - Increase in cell excitability,
prolongation.
HYPERKALEMIA
DEFINITION
Hyperkalemia is define as a serum potassium concentration greater than
5.5mEq/L. The normal serum concentration range for potassium is 3.5-
5.0mEq/L .
CLINICAL PRESENTATION OF HYPERKALEMIA GENERAL
Related to the effects of excessive k+ on neuromuscular, cardiac &
smooth muscle cell function
CLASSIFICATION

It can be classified according to severity

Mild hyperkalemia-5.5 6mEq/L

Moderate hyperkalemia-6.1-6.9mEq/L

Severe hyperkalemia->7
SYMPTOMS
Patient may complains of:-
• Dyspnea
• Heart palipitation/strpped heart beats.
• Nausea or Vomiting
• Chest pain, ECG changes
CAUSES
Increased potassium intake.
Decreased potassium excretion.
Tubular unresponseviness to aldosterone.
Redistribution of potassium into extracellular space.
Latrogenic cause like overreplacement with K/Cl and administration
of potassium containing medication (K penicillin) to susceptable
patients.
Increase intake of potassium in dite:
vegetables(tomatoes)&fruits(banana,citrus fruit)
INTRODUCTION
Endocrine function of pancreas is performed by the islets of Langerhans.
Human pancreas contains about 1 to 2 million islets. Islets of
Langerhans consist of four types of cells:
A cells or α-cells, which secrete glucagon
B cells or β-cells, which secrete insulin
D cells or δ-cells, which secrete somatostatin
F cells or PPcells, which secrete pancreatic polypeptide.
INSULIN
SOURCE OF SECRETION
Insulin is secreted by B cells orthe β-cells in the islets of Langerhans of
pancreas.
ACTIONS OF INSULIN
1. On Carbohydrate Metabolism
Insulin is the only antidiabetic hormone secreted in the body, i.e.
it is the only hormone in the body that reduces blood glucose level.
Insulin reduces the blood glucose level by its actions on carbohydrate
metabolism
2. On Protein Metabolism
Insulin facilitates the synthesis and storage of proteins and inhibits the
cellular utilization of proteins.
Cont...
3. On Fat Metabolism
Insulin stimulates the synthesis of fat. It also increases the storage of fat
in the adipose tissue.
Insulin promotes the storage of fat in adipose tissue by inhibiting
the enzymes which degrade the triglycerides. Insulin promotes the
transport of excess glucose into cells, particularly the liver cells.
4. On Growth
Along with growth hormone, insulin promotes growth of body by its
anabolic action on proteins.
BLOOD GLUCOSE

In normal persons, blood glucose level is controlled within a narrow

range. In the early morning after overnight fasting, the blood glucose
level is low ranging between 70 and 110 mg/dL of blood. Between first
and second hour after meals (postprandial), the blood glucose level
rises to 100 to 140 mg/dL.
DIABETES MELLITUS

Diabetes mellitus is a metabolic disorder characterized by high blood

glucose level, associated with other manifestations. ‘Diabetes’ means
‘polyuria’ and ‘mellitus’ means ‘honey’. The name ‘diabetes mellitus’
was coined by Thomas Willis, who discovered sweetness of urine from
diabetics in 1675.
CLASSIFICATION
Type I Diabetes Mellitus
Type Idiabetes mellitus is due to deficiency of insulin because of
destruction of β-cells in islets of Langerhans. This type of diabetes
mellitus may occur at any age of life.
Persons affected by this require insulin injection. So it is also called
insulin-dependent diabetes mellitus (IDDM). When it develops at
infancy or childhood, it is called juvenile diabetes.
Cont...
Type II diabetes mellitus

It is due to insulin resistance (failure of insulin receptors to give

response to insulin). So, the body is unable to use insulin. About 90%
of diabetic patients have type II diabetes mellitus. It usually occurs after
40 years. It can be controlled by oral hypoglycemic drugs. So it is also
called non insulin dependent diabetes mellitus (NIDDM).
Other forms of Type II DM
1. Gestational diabetes: It occurs during pregnancy. It is due to many
factors such as hormones secreted during pregnancy, obesity and
lifestyle before andduring pregnancy. Usually, diabetes disappears after
delivery of the child. However, the woman has high risk of development
of type II diabetes later.
2. Pre-diabetes: It is also called chemical, subclinical, latent or
borderline diabetes. It is the stage betweennormal condition and
diabetes.
COMPLICATIONS OF DM

1. Cardiovascular complications like:

i. Hypertension

ii. Myocardial infarction

2. Degenerative changes in retina called diabetic retinopathy

3. Degenerative changes in kidney known as diabetic nephropathy

4. Degeneration of autonomic and peripheral nerves called diabetic neuropathy

Signs and Symptoms of DM
Increased blood glucose level (300 to 400 mg/dL)due to reduced
utilization by tissue.
Glucosuria: It is the loss of glucose in urine. Normally, glucose does
not appear in urine. When glucose level rises above 180 mg/dL in blood
glucose appears in urine. It is the renal threshold level for glucose.
Polyuria: Excess urine formation with increase in the frequency of
voiding urine is called polyuria. It is due to the osmotic diuresis caused
by increase in blood glucose level.
Cont...
Polydipsia: Increase in water intake is called polydipsia. Excess loss
of water decreases the water content and increases the salt content in the
body. This stimulates the thirst center in hypothalamus. Thirst center, in
turn increases the intake of water.
Polyphagia: Polyphagia means the intake of excess food. It is very
common in diabetes mellitus.
Acidosis: During insulin deficiency, glucose cannot be utilized by the
peripheral tissues for energy. So, a large amount of fat is broken down
to release energy. It causes the formation of excess ketoacids, leading to
acidosis
Cont...
Acetone breathing: In cases of severe ketoacidosis, acetone is expired
in the expiratory air, giving the characteristic acetone or fruity breath
odor. It is a life-threatening condition of severe diabetes.
HYPERGLYCEMIA
Hyperglycemia is the medical term describing an abnormally high blood
glucose (blood sugar) level.
Hyperglycemia is a hallmark sign of diabetes (both type 1 diabetes
and type 2 diabetes) and prediabetes.
Diabetes is the most common cause of hyperglycemia.
The main symptoms of hyperglycemia are increased thirst and a
frequent need to urinate.
SIGN & SYMPTOMS
The main symptoms of hyperglycemia are increased thirst and a
frequent need to urinate.
Other symptoms that can occur with hyperglycemia are headaches,
tiredness, blurred vision, hunger, trouble with thinking or concentrating,
poor wound healing, dry or itchy skin etc.
PRECAUTIONS
ØFollow diabetes meal plan: The food you eat must be in balance with the insulin
working in your body.

ØIf blood sugar levels are above target range, drink extra liquids. This helps replace the
fluids lost through urine.

ØWater and sugar-free drinks are best. Drink non- caffeinated and non-alcoholic
beverages that do not contain sugar. avoid other drinks that have a lot of sugar, such
as fruit juice.

ØCheck blood sugar at home often.

HYPOGLYCEMIA

Hypoglycemia is the medical term describing an abnormally low

blood glucose (blood sugar) level.

Hypoglycemia occurs when blood glucose levels fall below 4 mmol/L

(72mg/dL).

Hypoglycemia can be a side effect of insulin or other types of diabetes

medicines that help your body make more insulin.
SIGN & SYMPTOMS

Confusion, heart palpitations, shakiness and anxiety.

Being pale, feeling weak and hungry, irritability.

Blurred visions Abnormal thinking, impaired judgment Nonspecific

dysphoria, moodiness, depression, crying, exaggerated concerns.

Fatigue, weakness, apathy, lethargy, daydreaming, sleep Confusion,

memory loss, lightheadedness or dizziness, delirium.
INVESTIGATIONS
• Plasma glucose level,
• Insulin level
• C-peptide level
• Proinsulin level
• Beta-hydroxybutyrate level
• Oral hypoglycemic agent screen
• Response of blood glucose level to glucagon
• Insulin antibodies
TREATMENT
After hypoglycemia in a person is identified, rapid treatment is
necessary and can be life-saving. The main goal of treatment is to raise
blood glucose back to normal level.
If an individual recognizes the symptoms of hypoglycemia coming on,
blood sugar should promptly be measured, and a sugary food or drink
should be consumed. The person must be conscious and able to swallow.
The goal is to consume 10–20 grams of a carbohydrate to raise blood
glucose levels to a minimum of 70 mg/dL
Cont...
The best way to consume a carbohydrate it to allow it to dissolve under
the tongue, also referred to as sublingual administration. For example, a
hard candy can be dissolved under the tongue, however the best
improvements in blood glucose will occur if the hard candy is chewed
and crushed, then swallowed.
OTHER TREATMENT
While the treatment of hypoglycemia is typically managed with
c a rbohydra t e c onsum pt i on, gl uc a gon i nj e c t i on , o r d e x t ro s e
administration, there are some other treatments available. Medications
like diazoxide and octreotide decrease insulin levels, increasing blood
glucose levels.