NEET MDS Synopsis
Red blood cell cycle
PhysiologyRed blood cell cycle:
RBCs enter the blood at a rate of about 2 million cells per second. The stimulus for erythropoiesis is the hormone erythropoietin, secreted mostly by the kidney. RBCs require Vitamin B12, folic acid, and iron. The lifespan of RBC averages 120 days. Aged and damaged red cells are disposed of in the spleen and liver by macrophages. The globin is digested and the amino acids released into the blood for protein manufacture; the heme is toxic and cannot be reused, so it is made into bilirubin and removed from the blood by the liver to be excreted in the bile. The red bile pigment bilirubin oxidizes into the green pigment biliverdin and together they give bile and feces their characteristic color. Iron is picked up by a globulin protein (apotransferrin) to be transported as transferrin and then stored, mostly in the liver, as hemosiderin or ferritin. Ferritin is short term iron storage in constant equilibrium with plasma iron carried by transferrin. Hemosiderin is long term iron storage, forming dense granules visible in liver and other cells which are difficult for the body to mobilize.
Some iron is lost from the blood due to hemorrhage, menstruation, etc. and must be replaced from the diet. On average men need to replace about 1 mg of iron per day, women need 2 mg. Apotransferrin (transferrin without the iron) is present in GI lining cells and is also released in the bile. It picks up iron from the GI tract and stimulates receptors on the lining cells which absorb it by pinocytosis. Once through the mucosal cell iron is carried in blood as transferrin to the liver and marrow. Iron leaves the transferrin molecule to bind to ferritin in these tissues. Most excess iron will not be absorbed due to saturation of ferritin, reduction of apotransferrin, and an inhibitory process in the lining tissue.
Erythropoietin Mechanism:
Myeloid (blood producing) tissue is found in the red bone marrow located in the spongy bone. As a person ages much of this marrow becomes fatty and ceases production. But it retains stem cells and can be called on to regenerate and produce blood cells later in an emergency. RBCs enter the blood at a rate of about 2 million cells per second. The stimulus for erythropoiesis is the hormone erythropoietin, secreted mostly by the kidney. This hormone triggers more of the pleuripotential stem cells (hemocytoblasts) to follow the pathway to red blood cells and to divide more rapidly.
It takes from 3 to 5 days for development of a reticulocyte from a hemocytoblast. Reticulocytes, immature rbc, move into the circulation and develop over a 1 to 2 day period into mature erythrocytes. About 1 to 2 % of rbc in the circulation are reticulocytes, and the exact percentage is a measure of the rate of erythropoiesis.
Cardiac Output
Physiology
Cardiac Output:
Minute Volume = Heart Rate X Stroke Volume
Heart rate, HR at rest = 65 to 85 bpm
Each heartbeat at rest takes about .8 sec. of which .4 sec. is quiescent period.
Stroke volume, SV at rest = 60 to 70 ml.
Heart can increase both rate and volume with exercise. Rate increase is limited due to necessity of minimum ventricular diastolic period for filling. Upper limit is usually put at about 220 bpm. Maximum heart rate calculations are usually below 200. Target heart rates for anaerobic threshold are about 85 to 95% of maximum.
Terms:
End Diastolic Volume, EDV - the maximum volume of the ventricles achieved at the end of ventricular diastole. This is the amount of blood the heart has available to pump. If this volume increases the cardiac output increases in a healthy heart.
End Systolic Volume, ESV - the minimum volume remaining in the ventricle after its systole. If this volume increases it means less blood has been pumped and the cardiac output is less.
EDV - ESV = SV
SV / EDV = Ejection Fraction The ejection fraction is normally around 50% at rest and will increase during strenuous exercise in a healthy heart. Well trained athletes may have ejection fractions approaching 70% in the most strenuous exercise.
Isovolumetric Contraction Phase - a brief period at the beginning of ventricular systole when all valves are closed and ventricular volume remains constant. Pressure has risen enough in the ventricle to close the AV valves but not enough to open the semilunar valves and cause ejection of blood.
Isovolumetric Relaxation Phase - a brief period at the beginning of ventricular diastole when all valves are closed and ventricular volume is constant. Pressure in the ventricle has lowered producing closure of the semilunar valves but not opening the AV valves to begin pulling blood into the ventricle.
Dicrotic Notch - the small increase in pressure of the aorta or other artery seen when recording a pulse wave. This occurs as blood is briefly pulled back toward the ventricle at the beginning of diastole thus closing the semilunar valves.
Preload - This is the pressure at the end of ventricular diastole, at the beginning of ventricular systole. It is proportional to the End Diastolic Volume (EDV), i.e. as the EDV increases so does the preload of the heart. Factors which increase the preload are: increased total blood volume, increased venous tone and venous return, increased atrial contraction, and the skeletal muscular pump.
Afterload - This is the impedence against which the left ventricle must eject blood, and it is roughly proportional to the End Systolic Volume (ESV). When the peripheral resistance increases so does the ESV and the afterload of the heart.
The importance of these parameters are as a measure of efficiency of the heart, which increases as the difference between preload and afterload increases
Graves disease
General Pathology
Graves disease
Graves disease is an organ-specific autoimmune disorder that results in thyrotoxicosis due to overstimulation of the thyroid gland by autoantibodies.
- It is the most common form of thyrotoxicosis, females being affected more than males by 8: 1.
- It is usually associated with a diffuse enlargement of the thyroid.
Pathogenesis
IgG-type immunoglobulins bind to TSH membrane receptors and cause prolonged stimulation of the thyroid, lasting for as long as 12 hours
(cf. 1 hour for TSH). The autoantibody binds at a site different to the hormone-binding locus and is termed the TSH-receptor autoantibody (TRAb); 95% of Graves’ disease patients are positive for TRAbs
Gross features
- The thyroid gland is diffusely and moderately enlarged
- It is usually smooth, soft, and congested
Histologically
- the gland shows diffuse hypertrophy and hyperplasia of acinar epithelium, reduction of stored colloid and local accumulations of lymphocytes with lymphoid follicle formation.
Clinical features
- Exophthalmos (protrusion of the eyeballs in their sockets)—due to the infiltration of orbital tissues by fat, mucopolysaccharides and lymphocytes. May cause compression of the optic nerve, hence blindness. However, only about 5% of Graves’ patients show signs of exophthalmos.
- Thyroid acropachy—enlargement of fingernails.
- Pretibial myxoedema—accumulation of mucoproteins in the deep dermis of the skin.
Treatment is as for thyrotoxicosis.
Biotin
Biochemistry
Biotin
Biotin helps release energy from carbohydrates and aids in the metabolism of fats, proteins and carbohydrates from food.
RDA The Adequate Intake (AI) for Biotin is 30 mcg/day for adult males and females
Biotin Deficiency Biotin deficiency is uncommon under normal circumstances, but symptoms include fatigue, loss of appetite, nausea, vomiting, depression, muscle pains, heart abnormalities and anemia.
Pancreas
Physiology
The bulk of the pancreas is an exocrine gland secreting pancreatic fluid into the duodenum after a meal. However, scattered through the pancreas are several hundred thousand clusters of cells called islets of Langerhans. The islets are endocrine tissue containing four types of cells. In order of abundance, they are the:
beta cells, which secrete insulin and amylin;
alpha cells, which secrete glucagon;
delta cells, which secrete somatostatin, and
gamma cells, which secrete a polypeptide of unknown function.
Beta Cells
Beta cells secrete insulin in response to a rising level of blood sugar
Insulin affects many organs. It
stimulates skeletal muscle fibers to
take up glucose and convert it into glycogen;
take up amino acids from the blood and convert them into protein.
acts on liver cells
stimulating them to take up glucose from the blood and convert it into glycogen while
inhibiting production of the enzymes involved in breaking glycogen back down (glycogenolysis) and
inhibiting gluconeogenesis; that is, the conversion of fats and proteins into glucose.
acts on fat (adipose) cells to stimulate the uptake of glucose and the synthesis of fat.
acts on cells in the hypothalamus to reduce appetite.
Diabetes Mellitus
Diabetes mellitus is an endocrine disorder characterized by many signs and symptoms. Primary among these are:
a failure of the kidney to retain glucose .
a resulting increase in the volume of urine because of the osmotic effect of this glucose (it reduces the return of water to the blood).
There are three categories of diabetes mellitus:
Insulin-Dependent Diabetes Mellitus (IDDM) (Type 1) and
Non Insulin-Dependent Diabetes Mellitus (NIDDM)(Type 2)
Inherited Forms of Diabetes Mellitus
Insulin-Dependent Diabetes Mellitus (IDDM)
IDDM ( Type 1 diabetes)
is characterized by little or no circulating insulin;
most commonly appears in childhood.
It results from destruction of the beta cells of the islets.
The destruction results from a cell-mediated autoimmune attack against the beta cells.
What triggers this attack is still a mystery, although a prior viral infection may be the culprit.
Non Insulin-Dependent Diabetes Mellitus (NIDDM)
Many people develop diabetes mellitus without an accompanying drop in insulin levels In many cases, the problem appears to be a failure to express a sufficient number of glucose transporters in the plasma membrane (and T-system) of their skeletal muscles. Normally when insulin binds to its receptor on the cell surface, it initiates a chain of events that leads to the insertion in the plasma membrane of increased numbers of a transmembrane glucose transporter. This transporter forms a channel that permits the facilitated diffusion of glucose into the cell. Skeletal muscle is the major "sink" for removing excess glucose from the blood (and converting it into glycogen). In NIDDM, the patient's ability to remove glucose from the blood and convert it into glycogen is reduced. This is called insulin resistance. NIDDM (also called Type 2 diabetes mellitus) usually occurs in adults and, particularly often, in overweight people.
Alpha Cells
The alpha cells of the islets secrete glucagon, a polypeptide of 29 amino acids. Glucagon acts principally on the liver where it stimulates the conversion of glycogen into glucose (glycogenolysis) which is deposited in the blood.
Glucagon secretion is
stimulated by low levels of glucose in the blood;
inhibited by high levels, and
inhibited by amylin.
The physiological significance of this is that glucagon functions to maintain a steady level of blood sugar level between meals.
Delta Cells
The delta cells secrete somatostatin. Somatostatin has a variety of functions. Taken together, they work to reduce the rate at which food is absorbed from the contents of the intestine. Somatostatin is also secreted by the hypothalamus and by the intestine.
Gamma Cells
The gamma cells of the islets secrete pancreatic polypeptide. No function has yet been found for this peptide of 36 amino acids.
Effects and Toxic Actions on Organ Systems
Pharmacology
Effects and Toxic Actions on Organ Systems
1. Local anesthetics (dose dependent) interfere with transmission in any excitable tissue (e.g. CNS and CVS).
2. CNS effects
a. Central neurons very sensitive.
b. Excitatory-dizziness, visual and auditory disturbances, apprehension, disorientation and muscle twitching more common with ester type agents.
c. Depression manifested as slurred speech, drowsiness and unconsciousness more common with amide type agents (e.g. lidocaine).
d. Higher concentrations of local anesthetic may eventually produce tonic-clonic[grand mal] convulsions.
e. Very large doses may produce respiratory depression which can be fatal. Artificial respiration may be life-saving.
3.CVS effects
a. Local anesthetics have direct action on the myocardium and peripheral vasculature by closing the sodium channel, thereby limiting the inward flux of sodium ions.
b. Myocardium usually depressed both in rate and force of contraction. Depression of ectopic pacemakers useful in treating cardiac arrhythmias.
c. Concentrations employed clinically usually cause vasodilation in area of injection.
d. Vasoconstrictors such as epinephrine may counteract these effects on myocardium and vasculature.
4. Local Tissue Responses
a. Occasionally focal necrosis in skeletal muscle at injection site, decreased cell motility and delayed wound healing.
b. Tissue hypoxia may be produced by action of excessive amounts of vasoconstrictors.
Hypoparathyroidism
General Pathology
Hypoparathyroidism
Hypoparathyroidism is a condition of reduced or absent PTH secretion, resulting in hypocalcaemia and hyperphosphataemia. It is far less common than hyperparathyroidism.
The causes of hypoparathyroidism are:
- Removal or damage of the parathyroid glands during thyroidectomy—most common cause of hypoparathyroidism resulting from inadvertent damage or removal.
- Autoimmune parathyroid disease—usually occurs in patients who have another autoimmune endocrine disease, e.g. Addison’s disease (autoimmune endocrine syndrome type 1).
- Congenital deficiency (DiGeorge syndrome)— rare, congenital disorder caused by arrested development of the third and fourth branchial arches, resulting in an almost complete absence of the thymus and parathyroid gland.
The effects of hypoparathyroidism are:
- ↓ release of Ca2+ from bones.
- ↓ Ca2+ reabsorption but ↑ PO 43− re absorption by the kidneys
- ↓ 1-hydroxylation of 25-hydroxyvitamin D by kidney.
Most symptoms of hypoparathyroidism are those of hypocalcaemia:
- Tetany—muscular spasm provoked by lowered plasma Ca 2+
- Convulsions.
- Paraesthesiae.
- Psychiatric disturbances, e.g. depression, confusional state and even psychosis.
- Rarely—cataracts, parkinsonian-like movement disorders, alopecia, brittle nails.
Management is by treatment with large doses of oral vitamin D; the acute phase requires intravenous calcium and calcitriol (1,25-dihydroxycholecalciferol, i.e. activated vitamin D).
Bones of the Skull
Anatomy
BONES OF THE CRANIUM
Occipital (1)
Frontal (1)
Sphenoid (1)
Ethmoid (1)
Parietal (2)
Temporal (2)
BONES OF THE FACE
Mandible (1)
Vomer (1)
Maxillae (2)
Zygomae (2)
Lacrimal (2)
Nasal (2)
Inferior nasal conchae (2)
Palatine (2)