The cretinism term is (obsolete ) replaced by the word ‘congenital iodine deficiency syndrome.’ The term cretin refers to a person suffering from cretinism that is not in vogue.
The ‘congenital iodine deficiency syndrome ‘ has features of
Physical growth retardation, and
Mental retardation.
Causes
The ‘congenital iodine deficiency syndrome is caused by extreme hypothyroidism during
Fetal life.
Infancy, and
Childhood’
This is due to deficiency of iodine in mother-Endemic cretinism in most cases. Goiter may be present.
Other etiological factors are rare; they occur.
Agenesis /hypogenesis of thyroid gland.
The ectopic thyroid gland, Congenital deficiency of some enzymes in thyroid hormone synthesis, and autoimmune thyroiditis may cause congenital iodine deficiency syndrome.
Sign and symptoms
Signs and symptoms are due to decreased thyroid hormones and are broadly grouped into physical and mental features.
Congenital iodine-deficiency syndrome is present at birth and characterized by retarded physical activity. Early diagnosis and treatment are essential to prevent intellectual damage. Neonatal screening is critical, and if there is evidence of thyroid hormone deficiency, treatment is started immediately as progressive mental -intellectual deterioration occurs with each passing week if not treated properly. Treatment in infancy will restore some physical changes but not the neural defects.
Treatment
Initiation of treatment with thyroxine 15 microgram /kg/day is recommended. Thyroxine tablet is crushed in a spoon and mixed with milk and given -tablet is tasteless and well accepted by infants.
Average thyroid hormone level is essential for brain development, neuron maturation, mental power, and the myelination process in the central nervous system. A progressive mental-intellectual deterioration occurs with each passing week if not treated properly.
Mental deterioration is widespread, and thoughts and reflexes become sluggish with reduced muscle tone. A person cannot speak in severe cases—incoordination of movements of varying degrees. The person cannot stand and walk and depends on others for primary care.
Cognitive defects are present.
Physical defects: Bone growth is more affected than soft-tissue growth. There is a disproportionate rate of change in soft tissue and skeletal tissue, causing excessive soft tissue enlargement. So, the child with congenital iodine deficiency syndrome is obese and stocky. The tongue becomes large and protrudes from the mouth. It may obstruct respiration and deglutition.It causes deep respiration and even chocks respiration.
Short stature, thick skin, hair loss, enlarged tongue, protruding abdomen. Delay in bone maturation.
Hypothyroidism is due to reduce hormone secretion by the thyroid gland for a prolonged time. Hypothyroidism is derived from the Greek words’ hypo-reduced, thyreos-shield, and eidos-‘form.’
Hypothyroidism is characterized by an increased level of TSH and the average level of T3 and T4. Subclinical hypothyroidism is more common than hypothyroidism.
Incidence of Hypothyroidism
About one billion people are suffering from iodine deficiency. But the incidence of hypothyroidism is not known.
Hypothyroidism occurs more in females than males.
People above 60 yrs are more commonly affected.
Causes
1. In developing countries, this is due to iodine deficiency.
2. In developed countries, hypothyreosis is due to the autoimmune disease Hashimoto’s thyroiditis.
3. Thyroid surgery
4. Radioactive iodine therapy
5. Congenital
6. Injury or diseases of the hypothalamus
7. Injury or diseases of the anterior lobe of the pituitary.
Types
The hypothalamo-pituitary-thyroid axis is responsible for the proper secretion of the thyroid hormones.
1. Primary hypothyroidism –The thyroid gland is not secreting hormones despite stimulation from ‘thyroid-stimulating hormone.’ This is the most typical type of hypothyroidism. Iodine deficiency is the commonest cause of primary hypothyroidism. Iodine deficiency is worldwide.
Thyroiditis of various causes, radioiodine treatment, thyroid surgery, thyroid dysgenesis.
2. Secondary hypothyroidism –The pituitary gland is not secreting ‘thyroid-stimulating hormone’ in an adequate amount. The causes are – pituitary adenoma, pituitary apoplexy, Sheehan syndrome, and subarachnoid hemorrhage.
3. Tertiary hypothyroidism: The hypothalamus does not secrete thyrotropin-releasing hormones in adequate amounts. This is an infrequent cause of hypothyroidism.
Increased secretion by the thyroid gland increases levels of ‘tri-iodo-thyronine’ T3 and ‘tetra-iodo-thyronine’ T4 in circulation. The high levels of the hormones cause hyperthyroidism.
When thyroid gland secretion increases due to autoimmunity, it is known as thyrotoxicosis or exophthalmic goiter.
Thyrotoxicosis is an auto-immune disorder in which ‘Thyroid stimulation antibodies ‘are formed by plasma cells after activation by antigens.
Thyroid stimulation antibodies (TSA), Long-acting thyroid stimulator( LATS), or Thyroid stimulating immunoglobins (TSI) are formed. It acts like normal TSH. The Long-acting thyroid stimulator or thyroid stimulation antibody (LATS, TSA) is IgG.
LATS protectors are produced, which protect the inactivation of LATS, so LATS functions are prolonged.
Mechanism of action:
LATS binds with TSH receptors present on the cell membrane of the thyroid cells by displacing the TSH. After combining with the receptor stimulates adenyl cyclase through Gs to form cyclic adenyl cyclase and activates Phosphorylase C like TSH. The cyclic adenyl cyclase activated Phosphorylase C performs many functions.
1. Increase T3 and T4 secretion by increasing iodide (I- ) trapping and transport mechanism.
2. Binding of iodide (I- ) to tyrosine.
3. Increase thyroglobulin synthesis in the colloid. The colloid iodide (I- ) gets oxidized immediately by ‘thyroid peroxidase’ into Iodine. First, Iodine binds to the third position of tyrosine to form ‘mono-iodo- tyrosine( MIT ), and in the next step, ‘mono-iodo- tyrosine( MIT )’ is iodinated at the fifth position to form ‘di-iodo- tyrosine( DIT ).’
Keywords: IGF-1 levels, gigantism, acromegaly level of IGF-1.
Table of contents:
1.
Introduction
2.
Incidence
3.
Features of Acromegaly Gigantism
4.
Causes
5.
Diagnosis
6.
Complications
7.
Treatment
Introduction :Abnormal excess secretion, i.e.hypersecretion of growth hormone, causes gigantism and acromegaly.
When hypersecretion of growth hormone occurs before the fusion of the long bones epiphysis leading to tall stature, hypersecretion of growth hormone causes increases in the size of bones. Therefore, before puberty, the growth hormone increases the length of bones leading to increased height and is called gigantism.
Acromegaly: hypersecretion of growth hormone after the fusion of the long bones epiphysis, i.e., after puberty, increases bone size, especially bones of hands, feet, and face. The condition is known as acromegaly.
Incidence : is very low only 0.001%. 10 new cases/1000,000 population.
Male and females are equally affected.
Usually appears in 5th decade of life.
Etilogy of Gigantism and acromegaly
Some genetic syndromes like neurofibromatosis, Carney complex, McCune-Albright syndrome, and Multiple endocrine neoplasias are associated with hypersecretion of the growth hormone.
1. Adenoma in the anterior pituitary gland is responsible for more than 95% of cases. In addition, familial idiopathic pituitary adenoma is responsible in some cases.
2. Excess secretion of ‘growth hormone-releasing hormone from a hypothalamic adenoma,
3. In some cases, neuroendocrine tumors from the lungs or pancreas secrete growth hormone-releasing hormone causing hypersecretion of Growth hormone.
4. In some cases, abdominal and other tumors can secrete ‘growth hormone-releasing, hormone causing hypersecretion of the growth hormone.
Features of acromegaly:
Acromegaly develops very slowly.
.
1. Enlargement of hands and feet due to bone thickness and soft tissue swelling. Bony changes are permanent. The extremities have a ‘dough-like consistency.
2. Increased sweating-hyperhidrosis.
3. Weakness, lethargy, kyphoscoliosis.
4. Acromegaly facies are characteristic of acromegaly. The features of acromegaly facies are a broad nose, large lips, enlarged tongue, coarsening of face, prominent supraorbital ridges, and enlarged jaw.
5. Deep voice
6. Obstructive sleep apnea.
Gigantism
Gigantism is a rare condition suspected when there is a rapid increase in the length of a person. Gigantism is usually associated with other syndromes, so features are multiple.
Diagnosis
1. EstimationofIGF-1 level is used to diagnose.
2. EstimationofGH levels is used to diagnose.
3. MRI and CT
3. Prolactin estimation.
4. Estimation of levelsof hormones of the anterior pituitary.
2. Radiation therapy if removal of adenoma is not possible.
3. Medical therapy is available-
Dopamine agonists-cabergoline is a D2 receptor agonist that acts on the D2 receptors in somatotrophs and decreases GH secretion.
GH receptor antagonists.
Complications
1. Cardiomyopathy
2. Hypertension
3. Arthropathy
4. Obstructive Sleep Apnea.
Hypopituitarism may occur due to surgery or radiation. Therefore, assessing hormones of anterior pituitary levels and hormone replacement may be needed.
Tags: Causes of acromegaly and gigantism #diagnosis #management#Hormones responsible for acromegaly#
Conn’s syndrome, primary hyperaldosteronism, or primary aldosteronism is due to excessive aldosterone secretion from the zona glomerulosa of the adrenal cortex.’
Cause: 1. Unilateral or bilateral adenoma of the zona glomerulosa of the adrenal cortex.
2. Rarely, it may be due to congenital defects.
3. Very rarely unilateral or bilateral cancerous growth of zona glomerulosa of the adrenal gland.
Signs and symptoms: Aldosterone controls sodium and potassium levels in the blood. Excess aldosterone causes increased sodium retention in the body and increased potassium excretion from the body.
Increased sodium retention in the body causes water retention and, therefore, increased blood pressure. The condition manifests as hypertension and complications of hypertension such as headache, stroke and heart attack, heart failure, and renal failure.
Increased potassium excretion from the body causes low potassium -hypokalemia. Features of hypokalemia manifest in (a) the heart, such as irregularities of the heart rhythm, and (b) the muscles, such as weakness, fatigue, inability to walk, and tetany.
Marked weakness
Polyuria -increased frequency of urination, polydipsia -increased and excessive thirst.
Hypertension
Tetany
Diagnosis
Increased level of aldosterone in plasma and urine(.normal level in plasma is 3-10 ng%)
2. Increased plasma level of sodium. (normal135-145 mEq/L)
3. Decreased plasma level of potassium ( normal3.5-5 mEq/l)
4. Features of metabolic alkalosis.
5. computerized tomography (CT) scan.
6. Magnetic resonance imaging(MRI)
Prognosis: Medical treatment: Conn’s syndrome can be managed by drugs.
Surgical treatment: surgical removal of adrenal gland tumor- adenoma can cure Conn’s syndrome.
Prevention: Conn’s syndrome can not be prevented.
Treatment:
Lifestyle changes are helpful-exercise, salt (sodium )restriction, potassium-rich fruits in the diet, no smoking, no alcohol, and no heavy work.
Definition: Addison’s disease is due to a deficiency of hormones (especially cortisol and aldosterone )secreted from the adrenal glands. This is also known as Addison disease, primary adrenal insufficiency, hypoadrenalism, hyporcorticism.
Incidence in India is less than one million cases per year. Drugs are very helpful in this incurable chronic disease.
Addison’s disease is characterized by adrenal insufficiency, especially hyposecretion of glucocorticoids. The disease is named to honor Thomas Addison, an English physician and scientist who described this disease.
1.
Definition
2.
Incidence in India and worldwide.
3.
Symptoms
4.
Signs
5.
Causes
6.
Diagnosis
7.
Treatment
Types
Addison’s disease is broadly classified into two groups :
Primary Addisons’ disease and
Secondary Addisons disease
Primary Addison’s disease is classified into
Idiopathic -Autoimmune disease and common in developed countries.
Infections: Generalised viral (cytomegalovirus ), fungal and tuberculous infections.
Iatrogenic: due to drugs: (ketoconazole) disease infection.or surgical removal of the adrenal gland.
Hemorrhage in both adrenal glands
Metastasis in both the adrenal glands.
Secondary adrenal insufficiency may be due to
Diseases of the anterior pituitary gland, therefore ACTH secretion is reduced.
Diseases of the hypothalamus that cause reduction of Corticiotrophic hormones (CTH).
Symptoms and signs:
1.Anorexia,nausea,vomiting,abdominal pain.
2. Weakness, lethargy. fainting attacks.
Hyperpigmentation of skin is usually more on skin exposed to sun rays, pressure points, and over the scars.
Hypoglycemia,hyponatremia,hypotension.
In stress conditions, a person suffering from Addison’s disease may develop acute Hypoglycemia and hypotension, known as Addison’s crisis. Addison’s crisis is a medical emergency, and if not treated promptly, it may cause death.
Diagnosis :
Physical examination -dark patches on the skin.
Serum electrolytes such as sodium,potassium levels.
Hormone estimation of cortisol,ACTH level.
X-rays -calcium deosits in the adrenal gland
ACTH stimulation test
CT scan
Treatment :
Hormone replacement therapy
In emergency vital sign supports are essential to support life.
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Here, you will find human Physiology,health-related topics, and general topics of public interest.
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Introduction
Plasma is blood from which formed elements of blood (red blood corpuscles (RBC), White blood corpuscles WBC), and platelets (thrombocytes) are removed.
Proteins present in the plasma are known as plasma proteins.
Average amount: 6.4 gm -8.3 gm per decilitre of blood.
Types:
Main:
Albumin 3-5 gm (4.8 gm )per decilitre of blood.
Globulin 2-3 gm per decilitre of blood.
Fibrinogen-0.3 gm per decilitre of blood.
Others:
Many other Plasma Proteins are present in tiny amounts.
Globulin from plasma cells, lymphocytes, tissue macrophages (reticuloendothelial system in liver, spleen, and bone marrow)
Whipple’s classification of cell proteins:
1. Labile Protein
2. Dispensable Protein
3. Indispensable protein or fixed cell protein.
Source of plasma protein:
Food protein, and in starvation tissue protein.
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If you have any medical issues, we advise you to seek the advice of a qualified doctor and follow their instructions.
A kidney is a bean-shaped structure with convex and concave borders. There is a recess in the concave wall known as renal-hilum, through which the renal artery enters and the renal vein and ureter exit. The weight of each kidney is about 150 grams. Each kidney is 10 cm long, 5 cm wide, and 2.5 cm thick- roughly about the size of a fist.
Gross structure of kidney: in the vertical section of the kidney, there are two layers:
Red outer cortex is more, and
Pale inner medulla is smaller than the cortex.The renal medulla receives little portion of the renl blood flow,but oxygen consumption is very high.It is very sensitive to hypoxia,hypotension and reduction of blood flow.(medulla renis in Latin means marrow of the kidney)
There are 10 to 15 pyramids in the medulla that terminate medially in the renal papilla and project in the minor calyces. The minor calyces join to form two major calyces which open in the renal pelvis. The renal pelvis continues as a ureter and ends in the urinary bladder.
Microscopic structure
In each kidney, 1 to 1.5 million nephrons are present. However, they are tiny, only 45 to 65 mm in length.
A detailed structure of the renal corpuscle- it has two components:
The renal corpuscle is the Bowman’s capsule and the glomerulus present in it.
Structure of the Glamorous
1. The glomerulus is a tuft of freely branching and anastomosing capillaries of the afferent arteriole. The capillaries join to form an efferent arteriole. About 30 loops of capillaries are present in one glomerulus.
This is one of the sites where an arteriole drains into arteriole. So blood from one arteriole passes into another arteriole.
The capillaries are fenestrated. The endothelial cell of the capillaries has multiple thousands upon thousands.’ The size of these pores ranges from 70 to 90 nanometers, allowing only particles of that size to pass through. Larger particles cannot pass through these pores. The capillaries rest on a basement membrane known as the ‘glomerular basement membrane.
Structure of the Glomerular Basement Membrane
The glomerular basement membrane is composed of three layers as recognized by the electron microscope:
Lamina densa is the thick, dense layer, surrounded by ‘lamina rara externa’ on the Bowman’s space side and ‘lamina rara interna’ towards the capillary side.
In other words, lamina densa is present in the center of the glomerular basement membrane.
Structure of Lamina Densa
Lamina densa comprises three peptide chains of the collagen type 4 collagen. There are six crucial isoforms of collagen Type 4. The isoforms are α-1 to α-6. Each isoform composes a triple helix structure in which the other two isoforms organize the collagen Type-4 network. α-3,4,5 isoforms form the triple helix. At the same time, α-1 and α-2 chains include mesangium.
The mesangium is essential for maintaining normal glomerular basement membrane integrity and becomes highly active in response to increased mechanical demands.
Many components are present in this highly cross-linked network, each with a specific function. For example, some structures include fibronectin, nidogen I &II, α-actinin, and laminin.
Lamininis an extracellular matrix glycoprotein.
The terminal parts of the three peptide chains are known as the ‘collagen component of collagen type 4. Antibody formation against these antigens may occur in some individuals, triggering the development of autoantibodies, specifically anti-glomerular basement membrane antibodies (anti-GBM).
This type of basement membrane is present in the basement membrane of other organs. The alveolar basement membrane structure is like that of the glomerular basement membrane.
Lamina rara externa and lamina rara interna
Lamina rara externa
The epithelial cells of the visceral layer of the Bowman’s capsule are present on the lamina rara externa. The lamina is composed of sialoglycoprotein-heparan sulfate. In addition, the lamina is rich in glycosaminoglycans -sulfated polysaccharides attached to a core protein known as Agrin.
Lamina rara interna
The lamina rara interna, lamina densa, and lamina rara externa are electronegative, repelling electronegative particles and attracting electropositive particles.
The epithelial cells have podocytes known as pedicles. The foot processes glue on the lamina and interdigitate to form the filtration slit. The size of the filtration slits ranges from 10 to 20 nanometers, preventing the passage of larger molecules.
The glomerular basement membrane is the main component of the glomerular filtration barrier and is responsible for ultrafiltration by the renal corpuscles. The glomerular basement membrane provides a barrier in two ways:
Size barrier, and
Charge selective barrier.
However, recent studies report that charge-selective permeability of the glomerular filtration barrier is not a significant barrier in glomerular filtration.
Types of collagen
Type 1 is present in bone, tendon, skin, and other organs
Type 2 is present in cartilage
Type 3 is widely present in the body as a reticulate
Type 4 is present in the basement membrane
Type 5 is present in cell surfaces and the Placenta.
The structure of the alveolar basement membrane is similar to that of the glomerular basement membrane. So the antibody developed against the glomerular basement membrane damages both the glomerular and alveolar basement membranes. This causes hematuria and hemoptysis. This occurs in Goodpasture syndrome along with other features.
Bowman’s Capsule
Bowman’s capsule is the initial dilated part of the nephron. It has two epithelial layers:
1. Visceral layer, and 2. Parietal layer.
The visceral layer is a part of the glomerular basement membrane. It is continuous with the parietal layer of the Bowman’s capsule at the entrance site of the afferent arterioles and exit of the efferent arterioles.
Parietal epithelial cell forms the outer lining of the Bowman’s capsule and are continuous with the visceral layer and the proximal convoluted tubule.
Bowman’s space is between the two layers of the Bowman’s capsule and is continuous with the proximal convoluted tubule lumen. The ultrafiltrate is collected in this space before passing to the proximal convoluted tubule.
The epithelial cells of the visceral layer of the Bowman’s capsule are present over the lamina rara externa. However, the epithelial cells are not continuous and give food processes known as pedicles. The pedicles interdigitate upon the lamina rara externa and form the filtration slit of 7-10 nm in size.
The filtration slit is guarded by a protein known as nephrin, allowing the passage of particles only 7-8 nanometers in size.
The renal corpuscle plays a crucial role in the ultrafiltration process, also known as hydrostatic filtration, of the plasma. Additionally, slight changes in the structure and electrical charges of the glomerular basement membrane can cause various diseases.
Size-dependent barriers
Layers of filtration:
1st: Fenestrated capillaries: 70-80 nanometers.
2nd filtration slits: 10-20 nanometers.
3rd nephrin 7-8 nanometer size.
Charge-related barriers
The lamina rara interna, lamina densa, and lamina rara externa are electronegative, repelling electronegative particles and attracting electropositive particles.
Therefore, electronegative plasma proteins are not filtered by normal glomerular basement membrane despite their small size.
The glomerular basement membrane is crucial for ultrafiltration, and any defect in this membrane results in the leakage of blood components.
Hormones and Enzymes are essential for the normal functioning of the human body. They are different from each other. Some significant differences are as follows:-
Hormones
Enzymes
1.
Hormones are produced by endocrine glands directly in the blood circulation
Enzymes are secreted from the exocrine gland and released in the ducts to reach the site.
2.
Hormones send messages to the tissues, trigger many functions, and are altered.
Enzymes are biocatalysts and increase biochemical reactions. However, they are not involved in the response and are not altered.
3.
Chemically hormones are protein, peptide, amine, and steroids.
Almost all enzymes are proteins. An exception is a ribonuclease.
4.
Hormones are not affected very much by the temperature and pH of body tissue.
Enzymes are affected by the temperature, pH of body tissue, and substrate concentration.
5.
Some hormones (steroids) diffuse in the cell and nucleus.
Enzymes are proteins and do not diffuse in the cell.
Details of hormones and enzymes are described in detail in my blog -https://totalphysiology.com. The link is given below.
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