Pathophysiology_FULL

29. General adaptation syndrome ( GAS). The stages and Selye’s triad of changes in special organs and systems. Adaptive hormones and their role in the

defensive reactions realizing in course of stress.

GAS – non-specific reaction of the whole organism to a stress situation.

30. Hypercortisolism. The main causes. Cushing’s syndrome: clinical features and their mechanisms.

The physiologic effects of glucocorticoids.

•1. Regulatory control of metabolism, water-electrolyte balance, functions of organs and systems.

•2. Anti-inflammatory and immunosuppressive effects.

(Secretion is regulated primarily by ACTH, which in turn is regulated by the CNS and hypothalamus by CRH, and feedback mechanism.)

Effects of  quantity of cortisol

Меchanism of arterial hypertension

1. sodium and water in blood   blood volume.

2.Permissive effect on catecholamines and on vascular tone.

3. Ca uptake in smooth muscle cells of vessels.

4. synthesis of endothelin,  synthesis of NO in endothelium.

5. synthesis of angiotensinogen, АCE и АТII.

6. NH3 (catabolism of proteins)   excitability of arterial pressure centre in CNS.

• 7. Blood analysis –

lymphopenia, eosinopenia, neitrophilia, eritrocytosis (Ht + water retention purple striae), reticulocytosis.

•8. Impaired cognitive function.

depression, emotional lability increased appetite ( obesity).

•9. Growth retardation in children - bone cells,GH, TSH secretion (partly) + excess of androgens  early puberty.

•10. Оsteoporosis – catabolic action of cortisol on bones (collagen and bone formation, bone resobtion)

•11. Anti-inflammatory effect.

•12. Immunosupression -  synthesis of AB,  activity of Т cells CD4, CD8, NK.

Cushing’s Disease.

1924 – Izenko N.M. reported about 2 patients with a damage to intermediate hypothalamus region.

1932 – Cushing H. described the clinical syndrome which he named «pituitary basophilism». Over 90% of patients with Cushing’s disease have a pituitary adenoma composed of basophilic corticotroph cells causing excessive secretion of ACTH. It is the most common cause of hypercortisolism.

Sometimes there is a connection between the disease and a head injury. CNS injury leads to  of dopamine activity then  inhibitory influence on CRH and ACTH secretion +  tone of serotoninergic system   secretion of cortisol (the «negative feedback» of the pituitary production of ACTH disappears).

31. Primary aldosteronism. The main causes. Clinical syndromes and their pathogenesis.

Hyperaldosteronism.

•Primary – Conn’s syndrome  aldosterone-secreting tumor of the adrenal cortex – aldosteroma, or bilateral hyperplasia of zona glomeruloza.

•Secondary hyperaldosteronism results from excessive renin production by the juxtaglomerular apparatus of the kidney. It is common compensatory reaction in many chronic diseases, which are accompanied by systemic edema (heart, sever liver, kidney diseases).

1.Patients are not edematous!!! (in contrast to patients with II hyperaldosteronism). blood volume and extracellular fluid volume lead to polyuria (8-10 l) and nocturia

(“escape” phenomenon from the action of aldosteron in collecting tubules;  secretion of atrial natriuretic peptide?).

2.Hypokalemic nephrophatyresistance to antidiuretic hormone (vasopressin)  polyuria, thirst, dehydration, (dry skin, decreased turgor).

Clinical features.

Hypertension, headache, thirst, polyuria, especially nocturia, tiredness, loss of stamina, weakness – all symptoms of K depletion. Paresthesias in different muscle groups, periodical muscle cramps, positive Chvostek and Trousseau sign.

Principles of therapy.

1.When aldosteroma – surgical removal only.

2.Lifelong treatment with aldosteron receptors blockers or with medical drugs that inhibit secretion of aldosteron.

32.Hypothyroidism. The main causes and specific syndromes. Characteristics of clinical features with their pathogenesis.

Physiological effects of thyroid hormones

•1. Heart. Chronotropic. Increase number and affinity of -adrenergic receptors.

Inotropic. Enhance responses to circulating catecholamines. Increase proportion of - myosin heavy chain (with higher АТP-аse activity).

•2. Adipose tissue. Catabolic - Stimulate lipolysis.

•3. Muscle. - Catabolic – increase protein breakdown.

•4. Nervous system. Promote normal brain development and functioning.

•5. Skeleton. Promote growth, development, metabolism, stimulate renewal of bones.

•6. Another tissues and organs. Calorigenic effect. Stimulate oxygen consuption by metabolically active tissues, increase metabolic rate.

The following diseases lead to hypothyroidism.

1.Thyroid surgery (thyroid ablation).

2.Endemic goiter.

3.Sporadic cretinism.

4.Hashimoto’s thyroiditis.

(all diseases – examples of primary hypothyroidism)

Clinical findings

•1. Often and typical symptom in severe hypothyroidism is myxedema - «mucous, pituitary edema»: diffuse, nonpitting puffiness of the skin. Similar edema develops in

the larynx, nose, GIT.



Accumulation of polysaccharides, chondroitin sulfuric acid, hyauluronic acid  Na and water retention( high hydrophilia of connective tissue),  lymphatic drain,  atrial Nauretic peptide, ADH, Na inand out cells, vascular permeability, ( Na in blood!).

•2.  basal metabolic rate  hypothermia, cold intolerance.

•3.  basal metabolic rate ( anabolism, catabolism)  weight gain, obesity; accumulation of metabolites:  cholesterol and triglycerides.

•4. CNS – apathy, forgetfulness, drowsiness; cretinism (inborn disease).

•5. Paresthesias, caused by compression neurophathies (myxedema).

•6. Dry and cold skin; dry and brittle hair, loss of body and scalp hair.

•7.  SV,  CO, bradycardia, diastolic pressure. [ number of -adrenergic receptors, myxedema, cardiomyopathy].

•8. Constipation (myxedema +  number of -adrenergic receptors).

•9. Edema (myxedema +  of diuresis, ANaUP).

•10.  growth and skeletal maturation (+ GH).

33. Hyperthyroidism. The main causes. Graves’ disease. Pathogenesis,clinical symptoms with their mechanisms of development.

•The autoimmune disease (II cytotoxic type according to Gell and Coombs).

•Аb = IgG (LATS-factor – Long-Acting Thyroid Stimulator). When it binds to the cell

membrane TSH receptors, TSH-R [stim] Ab stimulates hormone synthesis and secretion in the same way as TSH  thyrotoxicosis - diffuse toxic goiter (DTG). Glandular inflammation is absent.

Grave’s disease. Symptoms.

Classical triad: 1. Goiter. 2. Exophthalmos. 3. Palpitations.

+

4.Irritability, insomnia, muscular weakness.

5.Fine, pink, moist (sweaty) skin (heat loss).

6. temperature ( basal metabolism).

7.Тremor of hands.

8.Increased appetite. Weight loss.

9.Hyperdefecation ( frequency of bowel movements).

10.Pretibial myxedema = thyrotoxic dermopathy.

Exophthalmos.

•1. Proptosis develops in 25-50% in patients due to infiltration of orbital soft tissues and extraocular muscles with lymphocytes, mucopolysaccharides and edema fluid.

•2. This may lead to fibrosis of the extraocular muscles, restricted ocular motility, and diplopia.

•The wide-eyed star may be due to  sympathetic tone.

•In sever case pressure on the optic nerve or keratitis due to corneal exposure may lead to blindness.