Pathophysiology of endocrine system. (Subject 18)
2. Principles of hormone’s actionTypes of effects:
Endocrine effect (target cells are far from
Paracrine effect (target cells in the same
Autocrine effect (affection on the same cell
Interaction with receptors:
Receptors inside cells (influence on gene
Receptors on the cell surface (influence on
enzyme activity or ion channels).
3. Symptoms of endocrine disordersCommon symptoms:
alterations in height, weight, BMI
Principles of diagnostics:
blood plasma level
4. Endocrine Gland HypofunctionCongenital defects
absence or impaired development of the gland
absence of an enzyme needed for hormone
Destruction of gland
acute ischemia, trauma, hemorrhage
neoplastic growth (non-endocrine tumor or
5. Endocrine Gland HypofunctionProblems outside the endocrine gland:
understimulation by the pituitary
lack of substances needed for hormone synthesis
depression of hormones secretion by drugs or food
circulating antibodies against hormone
absence of receptor
antibodies to receptor
impaired cellular responsiveness to the hormone.
6. Endocrine Gland HypofunctionA decrease in
Lack of hormone
7. Endocrine Gland HyperfunctionCauses of increased hormone level:
overstimulation by the pituitary
hyperplasia or neoplasia of the gland
stimulation of gland by antibodies
rapid destruction of a gland
excess exogenous hormone administration.
8. General principles of therapyHypofunction:
replacement of the hormone
9. The levels of disordersHypothalamus
The levels of disorders
10. Pituitary disordersCauses :
11. Pituitary disordersGrowth hormone
children - short stature
adults - central obesity,
reduced muscle mass
and exercise capacity.
12. Pituitary disordersExcess of GH in childhood
proportional enlargement of
skeleton and inner organs
enlargement of the
delayed puberty and
13. Pituitary disordersExcess of GH in adults
reason –somatotrope adenoma
hyperplasia and hypertrophy of soft
size of hands, feet, nose, ears
cartilaginous proliferation of the
coarsening of the facial features.
enlarged tongue and increase of
thick and dark skin.
14. Pituitary disordersGH excess – Metabolic disturbances
GH and IGF-1.
synthesis of lipids in adipocytes, lipolysis and
free fatty acids level in blood plasma, of
glycogen in hepatocytes
tolerance to carbohydrates and diabetes
CVS - hypertension, cardiomegaly, heart failure
hyperphosphatemia ( tubular reabsorption of
15. Pituitary disordersExcess of ACTH - Cushing’s
High ACTH levels bilateral
Melanocyte stimulation by ACTH
hyperpigmentation of skin
cortisol due to adrenocortical
16. Cushing disease/syndromeClinical manifestation:
"moon" face and "buffalo hump“.
muscle wasting and weakness - due to
hypokalemia and glucose level in the
atrophic skin, with poor wound healing and
activation of protein catabolism and of
proteins synthesis in the skin.
17. Cushing disease/syndromeHypertension – due to water and salt
retention, vessels tone.
Osteoporosis – catabolism in the bone
high blood level of calcium.
Hyperglycemia, and diabetes mellitus – due
to contrinsular effect of cortizol.
Secondary immune deficiency – of immune
cells activity by cortizol
Signs of virilism in the female – of
androgens in addition to cortisol.
18. Pituitary disordersLack of ADH - Diabetes insipidus - polyuria,
Central Diabetes insipidus – lack of ADH (trauma,
Nephrogenic Diabetes insipidus DI - inability of the
kidney to respond normally to ADH.
Excess of ADH - Syndrome of Inappropriate ADH
(decreased excretion of free water).
production of ectopic ADH or ADH-like substance by
19. Thyroid disordersThyroid Hormone Action:
adequate fetal growth
development of neural and skeletal systems.
regulation of BMR and O2 consumption.
sympathetic effect on myocardium
20. Thyroid disordersGoiter - size of the thyroid gland.
(not related of TH level)
Complications of goiter:
difficulty in swallowing,
distention of the veins of the
neck and upper extremities,
edema of the eyelids and
syncope with coughing.
21. Thyroid disordersCongenital hypothyroidism cretinism
congenital absence of the
abnormal biosynthesis of
deficient TSH secretion.
Clinics: mental retardation,
22. Thyroid disordersAcquired hypothyroidism –
accumulation of a
substance in the connective
destruction or dysfunction
of the thyroid gland,
impaired pituitary function
23. Thyroid disordershypometabolic state
weakness and fatigue,
tendency to gain weight,
decreased GIT motility,
mental dullness, impaired memory
hoarse and husky voice,
pericardial or pleural effusion,
bradicardia, cardiac dilatation
24. Thyroid disordersHyperthyroidism –
antibodies act through the
normal TSH receptors and
cause thyroid hyperfunction
25. Thyroid disordersClinical manifestation:
BMR and heat production, heat intolerance
prevailing of sympathetic influences
warm and moist skin, perspiration
gases turnover in the lungs and dyspnea
GIT motility and diarrhea.
alterations in adrenal function
26. Thyroid disordersClinical manifestation:
tachycardia, of stroke volume
hypertension, widening of the pulse pressure
heart failure with minute blood volume.
weight loss despite increased appetite.
CNS - excitability, nervousness, insomnia
tremor and weakness of the muscles
27. Parathyroid disordersHypoparathyroidism reasons
surgical removal of the gland
Di George's syndrome
Low calcium, high phosphate
increased neuromuscular excitability tetany
ECG changes - prolonged Q-T S-T,.
28. Parathyroid disordersHyperparathyroidism
Chronic renal insufficiency
Vitamin D deficiency;
Hypercalcemia due to:
Ca renal reabsorption
intestinal calcium absorption
29. HyperparathyroidismClinical manifestations:
disturbances of excititation in nervous system
metastatic calcification of soft tissues,
hypertension, and heart palpitations,
increase of gastric secretion
30. Pathology of adrenal glandHypofunction of adrenal cortex (cortisol,
Primary adrenal hypofunction - ADDISON'S
Cause: atrophy of the adrenal cortex as a
tumor or metastatic disease
31. Hypofunction of adrenal cortexAldosterone deficiency
excretion of Na and excretion of K,
low blood concentrations of Na and Cl and a high
concentration of serum K.
severe dehydration, plasma hypertonicity,
decreased circulatory volume, hypotension.
disturbances in carbohydrate, fat, and protein
low resistance to infection, trauma, and other stress
hyperpigmentation of skin and mucous membranes
32. Addison's disease clinical manifestationWeakness, fatigue
GIT: anorexia, nausea, vomiting, diarrhea
Heart activity disturbances
Weight loss, dehydration, hypotension
33. Acute adrenal failure – Adrenal crisisCauses:
hemorrhage (overdose of heparine, acute or
dehydration of the organism;
insufficiency of bloodflow on all the levels
(results in patient’s death).
34. Hypofunction of adrenal cortexSecondary hypofunction - due to a lack of ACTH.
destruction of the pituitary;
long term steroid administration.
Patients are not hyperpigmented,
The disturbances of water and electrolyte levels are
In the case of panhypopituitarism – concomitant
depressed thyroid and gonadal function
35. Hyperfunction of adrenal cortexCauses
congenital adrenal hyperplasia,
acquired hyperplasia, adenomas, or adenocarcinomas.
ADRENAL VIRILISM (Adrenogenital Syndrome) excess of androgens.
Clinical signs in women:
deepening of the voice,
amenorrhea, atrophy of the uterus,
36. HyperaldosteronismPrimary HyperAldosteronism - Conn's Syndrome
Cause: tumor of the adrenal cortex or benign adrenal
Blood analysis: Na, Cl, K, hypervolemia.
muscular weakness, paresthesias, transient
paralysis, and tetany.
hypokalemic nephropathy with polyuria and
Hypernatremia and hypervolemia hypertension.
low or normal plasma rennin activity
37. HyperaldosteronismSecondary hyperaldosteronism is caused by
low blood circulating volume or low ABP
cirrhosis with ascites,
the nephrotic syndrome,
reduced renal blood flow due to
obstructive renal artery disease (eg, atheroma,
renal vasoconstriction (as occurs in