স্পেশাল বিসিএস (স্বাস্থ্য) - লং কোর্স

  Nonspecific laboratory findings associated with hypothyroidism.
Ø  Increased serum total cholesterol and LDL-C

Ø  Increased TAG (Triacyl glycerol)

Ø  Hyponatremia (due to free water retention)

Ø  Increased CPK (due to myopathy)

 Nonspecific laboratory findings associated with hyperthyroidism

Ø  Decreased serum cholesterol, LDL-C & TAG.

Ø  Increased CPK (due to myopathy)

Ø  Hepatic dysfunction, e.g. raised ALT and ALP

Graves’ disease
Definition: It is an autoimmune disease in which circulating antibodies are formed against the TSH receptor and activates the thyroid gland hyperactive, resulting in development of goiter and hypersecretion of T3 & T4
More common in women

Clinical features:
1.  Goiter with bruit
2.  Exophthalmos-protrusion of the eye ball (it is the hallmark of Graves' disease)
3.  Retraction of upper eye lid, lid lag
4.  Corneal ulceration
5.  Diplopia
6.  Ophthalmoplegia
7.  Papilledema
8.  Loss of visual acuity
9.  Vitiligo
10.  Digital clubbing
11.  Pretibial myxedema

 

Primary hyperparathyroidism (PHP)

 Definition: It is the hypercalcemic disorder due to excessive secretion of PTH.

Causes:
1. Parathyroid adenoma (80 %).

2. Primary hyperplasia of parathyroid gland (15 %). 3.Parathyroid carcinoma.

Average
Range
Total plasma Calcium concentration
2.4 mmol/L,or
4.8 mEq/L or,
9.4 mg/dl
2.2-2.6 mmol/L
8.5-10.5 mg/dl

Effects of low ionized Ca2+
1.  Increased excitability of nerve & muscles.
2.  Increased membrane permeability
3.  Impaired blood clotting
4.  Tetany
5.  Rickets (in children)
6.  Osteomalacia (In adult)

Glucocorticoid secretion unaffected
-High potassium intake
-Low sodium intake
-Constriction of inferior vena cava in thorax
-Standing
-Secondary hyperaldosteronism (In some cases of congestive heart failure, cirrhosis, and nephrotic syndrome)

With renin high and aldosterone high (secondary hyperaldosteronism)
• Inadequate renal perfusion, e.g. diuretic therapy, cardiac failure, liver failure, nephrotic syndrome, renal artery stenosis.
• Renin-secreting renal tumor (very rare)

With renin low and aldosterone high (primary hyperaldosteronism)
·         Adrenal adenoma secreting aldosterone (Conn's syndrome)
·         Idiopathic bilateral adrenal hyperplasia
·         Glucocorticoid-suppressible hyperaldosteronism (rare)

Metabolic actions of glucocorticoids Effects On carbohydrate  -Promotion of gluconeogenesis
Metabolism - (cortisol stimulates synthesis of gluconeogenic enzyme by DNA transcription)
-  Reduction in glucose utilization
-  Increase deposition of liver glycogen
-Block glucose transport in muscle and
-Adipose tissue (anti insulin action)
Net effect: increased blood glucose

Stress management (fight & flight response to face sudden emergency) by:
Ø  Gluconeogenesis that provides glucose to be used as fuel in neurons.
Ø  Proteolysis that provides amino acid to support gluconeogenesis and acute phase protein synthesis in liver.
Ø  Lipolysis that provides fatty acid to be used as fuel in peripheral tissues.
Ø  Maintenance of ECF volume and blood pressure.

* For these functions in relation to stress, cortisol is called emergency hormone

Hematopoietic function of cortisol
·         BEL ↓ (basophil, Eosinophil, Lymphocyte)

·         PEN ↑ (Platelet, erythrocyte, neutrophil)

 Laboratory findings in Cushing's syndrome:
1.  Urinary free cortisol excretion increases (normal < 100ug/day).
2.  Plasma cortisol increases (normal 10ug/dl, average).
3.  Dexamethasone suppression test (DST).
Here synthetic steroid (dexamethasone) is given which is expected to reduce ACTH and cortisol secretion by negative feedback. Normally plasma cortisol decreases, but failure of plasma cortisol reduction following DST suggests Cushing's syndrome.
4. Plasma ACTH (normal = 9.52 pg/L)
Moderately increaed in Cushing's disease, markedly increased in ectopic ACTH and very low or undetectable in adrenal tumor.

Metabolic features:
1.  Dilutional hyponatremia, hyperkalemia and metabolic acidosis.
2.  Marked insulin sensitivity and hypoglycemia.
3.  Renal salt and water loss, hypotension & weight loss.
4.  Hyperpigmentation of skin and buccal mucosa (due to increased ACTH following decreased cortisol).
5.  Adrenal crisis (Addisonian crisis)
It is the state of acute adrenocortical insufficiency in patients with Addison’s disease who are exposed to the stressful conditions like infection, trauma surgery, vomiting, diarrhoea etc. Patients become confused, disoriented and eventually develop severe hypotension and shock.

Ref: ABC 6th/P-510

Primary (ACTH) Addison's disease Common causes
·       Autoimmune
o   Sporadic
o   Polyglandular syndromes
·       Tuberculosis
·       HIV/AIDS
·       Metastatic carcinoma
·       Bilateral adrenalectomy
Rare causes
·       Lymphoma
·        Intra-adrenal hemorrhage (Waterhouse-Friedrichsen syndrome following meningococcal sepsis)
·       Amyloidosis
·       Haemochromatosis

Laboratory findings in Conn's syndrome:
1.  Urinary potassium excretion increases
2.  Increased plasma aldosterone with decreased plasma renin concentration.
3.  Urinary aldosterone excretion increases.
4.  Hypokalemia.

 Functions of ACTH:
1.  Growth of adrenal cortex.
2.  Stimulation of glucocorticoid secretion.
3.  Mild stimulation of adrenal androgen secretion.
4.Stimulates melanocytes and causes skin pigmentation

Effects of insulin on various tissues
Adipose tissue
Increased glucose entry Increased fatty acid
Increased glycerol phosphate synthesis Increased triglyceride deposition Activation of lipoprotein lipase Inhibition of hormone sensitive lipase Increased K+ uptake
Muscle
Increased glucose entry Increased glycogen synthesis Increased amino acid uptake
Increased protein synthesis in ribosomes Decreased protein catabolism
Decreased release of gluconeogenic amino acids Increased ketone uptake
Increased K+ uptake

Insulin causes hypoglycemia by:
1.  Uptakes & oxidation of glucose by cells
2.  Uptake & storage of glucose as glycogen in muscle & liver.
3.  Uptake & utilization of glucose for lipogenesis & fat synthesis in adipocyte.
4.  Inhibition of gluconeogenesis & glycogenolysis

Hormones that counteract the action of insulin Diabetogenic hormones:
1.  Glucagon
2.  Cortisol
3.  Epinephrine & Norepinephrine
4.  Growth hormone
5.  Thyroid hormone

GLUT 5
Fructose transport
Jejunum, sperm, intesti

How to perform an oral glucose tolerance test (OGTT)
Preparation before the test
·       Unrestricted carbohydrate diet for 3 days
·       Fasted overnight for at least 8 hrs
·       Rest for 30 mins
·       Remain seated for the duration of the test, with no smoking

Sertoli cells
1.       Inhibin
2.       Androgen-binding protein (ABP)
3.       Mullerian inhibiting substance (MIS)
4.       Estrogen