NEET MDS Synopsis
B-Oxidation Pathway:
Biochemistry
Step 1. Acyl-CoA Dehydrogenase catalyzes oxidation of the fatty acid moiety of acyl-CoA, to produce a double bond between carbon atoms 2 and 3.
There are different Acyl-CoA Dehydrogenases for short (4-6 C), medium (6-10 C), long and very long (12-18 C) chain fatty acids. Very Long Chain Acyl-CoA Dehydrogenase is bound to the inner mitochondrial membrane. The others are soluble enzymes located in the mitochondrial matrix.
FAD is the prosthetic group that functions as electron acceptor for Acyl-CoA Dehydrogenase.
A glutamate side-chain carboxyl extracts a proton from the a-carbon of the substrate, facilitating transfer of 2 e- with H+ (a hydride) from the b position to FAD. The reduced FAD accepts a second H+, yielding FADH2
The carbonyl oxygen of the thioester substrate is hydrogen bonded to the 2'-OH of the ribityl moiety of FAD, giving this part of FAD a role in positioning the substrate and increasing acidity of the substrate a-proton
The reactive glutamate and FAD are on opposite sides of the substrate at the active site. Thus the reaction is stereospecific, yielding a trans double bond in enoyl-CoA.
FADH2 of Acyl CoA Dehydrogenase is reoxidized by transfer of 2 electrons to an Electron Transfer Flavoprotein (ETF), which in turn passes the electrons to coenzyme Q of the respiratory chain.
Step 2. Enoyl-CoA Hydratase catalyzes stereospecific hydration of the trans double bond produced in the 1st step of the pathway, yielding L-hydroxyacyl-Coenzyme A
Step 3. Hydroxyacyl-CoA Dehydrogenase catalyzes oxidation of the hydroxyl in the b position (C3) to a ketone. NAD+ is the electron acceptor.
Step 4. b-Ketothiolase (b-Ketoacyl-CoA Thiolase) catalyzes thiolytic cleavage.
A cysteine S attacks the b-keto C. Acetyl-CoA is released, leaving the fatty acyl moiety in thioester linkage to the cysteine thiol. The thiol of HSCoA displaces the cysteine thiol, yielding fatty acyl-CoA (2 C shorter).
A membrane-bound trifunctional protein complex with two subunit types expresses the enzyme activities for steps 2-4 of the b-oxidation pathway for long chain fatty acids. Equivalent enzymes for shorter chain fatty acids are soluble proteins of the mitochondrial matrix.
Summary of one round of the b-oxidation pathway:
fatty acyl-CoA + FAD + NAD+ + HS-CoA →
fatty acyl-CoA (2 C shorter) + FADH2 + NADH + H+ + acetyl-CoA
The b-oxidation pathway is cyclic. The product, 2 carbons shorter, is the input to another round of the pathway. If, as is usually the case, the fatty acid contains an even number of C atoms, in the final reaction cycle butyryl-CoA is converted to 2 copies of acetyl-CoA
ATP production:
FADH2 of Acyl CoA Dehydrogenase is reoxidized by transfer of 2 e- via ETF to coenzyme Q of the respiratory chain. H+ ejection from the mitochondrial matrix that accompanies transfer of 2 e- from CoQ to oxygen, leads via chemiosmotic coupling to production of approximately 1.5 ATP. (Approx. 4 H+ enter the mitochondrial matrix per ATP synthesized.)
NADH is reoxidized by transfer of 2 e- to the respiratory chain complex I. Transfer of 2 e- from complex I to oxygen yields approximately 2.5 ATP.
Acetyl-CoA can enter Krebs cycle, where the acetate is oxidized to CO2, yielding additional NADH, FADH2, and ATP.
Fatty acid oxidation is a major source of cellular ATP
b-Oxidation of very long chain fatty acids also occurs within peroxisomes
FAD is electron acceptor for peroxisomal Acyl-CoA Oxidase, which catalyzes the first oxidative step of the pathway. The resulting FADH2 is reoxidized in the peroxisome producing hydrogen peroxide FADH2 + O2 à FAD + H2O2
The peroxisomal enzyme Catalase degrades H2O2 by the reaction:
2 H2O2 → 2 H2O + O2
These reactions produce no ATP
Once fatty acids are reduced in length within the peroxisomes they may shift to the mitochondria to be catabolized all the way to CO2. Carnitine is also involved in transfer of fatty acids into and out of peroxisomes
Hyperthyroidism
General Pathology
Hyperthyroidism
Hyperthyroidism (Thyrotoxicosis) is a hypermetabolic state caused by elevated circulating levels of free T3 and T4 . This may primary (Graves disease) or rarely, secondary (due to pituitary or hypothalamic diseases).
- The diagnosis is based on clinical features and laboratory data.
Lab Test
- The measurement of serum TSH concentration provides the most useful single screening test for hyperthyroidism, because TSH levels are decreased in primary cases, even when the disease is still be subclinical.
- In secondary cases TSH levels are either normal or raised.
- A low TSH value is usually associated with increased levels of free T4 .
- Occasionally, hyperthyroidism results from increased levels of T3 .
Growth and spread of tumours
General Pathology
Growth and spread of tumours
Growth in excess of normal is a feature of all tumours but extension to tissue away from the site of origin is a feature of malignant tumours.
Modes of spread of malignant tumours
- local, invasion. This is a feature of all malignant tumors and takes place along tissue spaces and facial planes
o Lymphatic spread. Most often seen in carcinomas. This can be in the form of
o Lymphatic permeation: Where the cells extend along the lymphatics as a solid core
o Lymphatic embolisation: Where a group of tumour cells break off and get carried to the draining mode
-Vascular spread : This is a common and early mode of spread for sarcomas but certain carcinomas like renal cell carcinoma and chorio carcinoma have a predilection to early vascular spread.
Vascular spread is most often due .to invasion of venous channels and can be by permeation or embolisation.
Lungs, liver, bones and brain are the common sites for vascular metastasis but
different tumours have different organ preference for metastasis, e.g. : Bronchogenic carcinoma often spreads to liver and adrenals.
-Body cavities and natural passages
o Gastrointestinal carcinomas spread to ovaries (Krukenberg’s tomour)
Enflurane
Pharmacology
Enflurane (Ethrane) MAC 1.68, Blood/gas solubility ratio 1.9
- Extremely stable chemically.
- Less potent and less soluble in blood than is halothane.
- Respiratory depression is similar to that seen with halothane.
- Cardiac output is not depressed as much as with halothane, and the heart is not sensitized to catecholamines to the same degree.
- Enflurane produces better muscle relaxation than does halothane.
- Metabolism of this agent is very low. Inorganic fluoride is a product of metabolism, but is not sufficient to cause renal problems.
- Enflurane differs from halothane and the other inhalational anesthetic agents by causing seizures at doses slightly higher than those that induce anesthesia.
- Nausea appears to occur somewhat more often following Enflurane than it does following halothane.
Functional Divisions of the Nervous System
PhysiologyFunctional Divisions of the Nervous System:
1) The Voluntary Nervous System - (ie. somatic division) control of willful control of effectors (skeletal muscles) and conscious perception. Mediates voluntary reflexes.
2) The Autonomic Nervous System - control of autonomic effectors - smooth muscles, cardiac muscle, glands. Responsible for "visceral" reflexes
HEART DISORDERS
Physiology
HEART DISORDERS
Pump failure => Alters pressure (flow) =>alters oxygen carrying capacity.
Renin release (Juxtaglomerular cells) Kidney
Converts Angiotensinogen => Angiotensin I
In lungs Angiotensin I Converted => Angiotensin II
Angiotensin II = powerful vasoconstrictor (raises pressure, increases afterload)
stimulates thirst
stimulates adrenal cortex to release Aldosterone
(Sodium retention, potassium loss)
stimulates kidney directly to reabsorb Sodium
releases ADH from Posterior Pituitary
Myocardial Infarction
Myocardial Cells die from lack of Oxygen
Adjacent vessels (collateral) dilate to compensate
Intracellular Enzymes leak from dying cells (Necrosis)
Creatine Kinase CK (Creatine Phosphokinase) 3 forms
One isoenzyme = exclusively Heart (MB)
CK-MB blood levels found 2-5 hrs, peak in 24 hrs
Lactic Dehydrogenase found 6-10 hours after. points less clearly to infarction
Serum glutamic oxaloacetic transaminase (SGOT)
Found 6 hrs after infarction, peaks 24-48 hrs at 2 to 15 times normal,
SGOT returns to normal after 3-4 days
Myocardium weakens = Decreased CO & SV (severe - death)
Infarct heal by fibrous repair
Hypertrophy of undamaged myocardial cells
Increased contractility to restore normal CO
Improved by exercise program
Prognosis
10% uncomplicated recovery
20% Suddenly fatal
Rest MI not fatal immediately, 15% will die from related causes
Congenital heart disease (Affect oxygenation of blood)
Septal defects
Ductus arteriosus
Valvular heart disease
Stenosis = cusps, fibrotic & thickened, Sometimes fused, can not open
Regurgitation = cusps, retracted, Do not close, blood moves backwards
Cells Of The Exudate
General Pathology
Cells Of The Exudate
Granulocytes (Neutrophils, eosinophils, and basophils)
Monocytes (and tissue macrophages)
Lymphocytes
Neutrophils (polymorphs).
Characteristics
(1) Cell of acute inflammation.
(2) Actively motile.
(3) Phagocytic.
(4) Respond to chemotactic agents like.
Complement products.
Bacterial products.
Tissue breakdown
Lysosomal enzymes of other polymorphs
Functions
(1) Phagocytosis and intracellular digestion of bacteria.
(2) Exocytosis of lysosomal enzymes to digest dead tissue as the first step in the process of repair.
Eosinophils
Characteristics
(I) Cell of allergjc and immunologic inflammation.
(2) Motile and phagocytic but less so than a neutrophil.
(3) Response to chemotaxis similar to neutrophil. In addition, it is also responsive to antigens and antigen-antibody complexes.
(4) Steroids cause depletion of eosinophils.
Functions
(1) Contain most of the lysosomal enzymes that polymorphs have
(2) control of Histamine release and degradation in inflammation
Basophils (and mast cells)
Characteristics
(1) Contain coarse metachromatic granules.
(2) Contain, histamine and proteolytic enzymes
Functions
Histamine: release which causes some of the changes of inflammation and allergic
reactions. .
Monocytes .
Blood monocytes form a component of. the mononuclear phagocytic system (MPS), the other being tissue macrophages The tissue macrophages may be :
(a) Fixed phagocytic. cells:
Kuffer cell of liver.
Sinusoidal lining cells of spleen and lymph nodes.
Pleural and peritoneal macrophages
Alveolar macrophages.
Microglial cells.
(b) Wandering macrophages or tissue histiocytes.
The tissue histiocytes are derived from blood monocytes.
Characteristics
.(1)Seen in inflammation of some duration, as they -outlive polymorphs.
(2) Actively phagocytic and motile.
(3) Fuse readily to from giant cells in certain situations.
Function
(1) Phagocytosis.
(2) Lysosomal enzyme secretion.
(3) Site of synthesis of some components of complement.
(4) Antigen handling and processing before presenting it to the Immune competent cell.
(5) Secretion of lysosyme and interferon.
Giant cells can be
(A) Physiological
Syncytiotrophoblast, megakatyocytes, striated muscle, osteoclast.
(B) Pathological:
Foreign body: in the presence of particulate foreign matter like talc, suture material etc. and in certain infections_e g fungal.
Langhan's type: a variant of foreign body giant cell seen in tuberculosis.
Touton type in lipid rich situations like Xanthomas, lipid granulomas etc.
(iv) Aschoff cell in rheumatic carditis.
(v) Tumour gjant cells e.g. Reid-Sternberg cell in Hodgkin's Lymphoma, giant cells in any malignancy.
Lymphocytes and Plasma cells
These are the small mononuclear cell comprising the immune system
They are less motile than_macrophages and neutrophils and are seen in chronic inflammation and immune based diseases.
Mandibular Tori
Oral and Maxillofacial SurgeryMandibular Tori
Mandibular tori are bony growths that occur on the mandible,
typically on the lingual aspect of the alveolar ridge. While they are often
asymptomatic, there are specific indications for their removal, particularly
when they interfere with oral function or prosthetic rehabilitation.
Indications for Removal
Interference with Denture Construction:
Mandibular tori may obstruct the proper fitting of full or partial
dentures, necessitating their removal to ensure adequate retention and
comfort.
Ulceration and Slow Healing:
If the mucosal covering over the torus ulcerates and the wound
exhibits extremely slow healing, surgical intervention may be required
to promote healing and prevent further complications.
Interference with Speech and Deglutition:
Large tori that impede normal speech or swallowing may warrant
removal to improve the patient's quality of life and functional
abilities.
Surgical Technique
Incision Placement:
The incision should be made on the crest of the ridge if
the patient is edentulous (without teeth). This approach allows for
better access to the torus while minimizing trauma to surrounding
tissues.
If there are teeth present in the area, the incision should be made
along the gingival margin. This helps to preserve the
integrity of the gingival tissue and maintain aesthetics.
Avoiding Direct Incision Over the Torus:
It is crucial not to make the incision directly over the torus.
Incising over the torus can lead to:
Status Line: Leaving a visible line on the
traumatized bone, which can affect aesthetics and function.
Thin Mucosa: The mucosa over the torus is
generally very thin, and an incision through it can result in
dehiscence (wound separation) and exposure of the underlying bone,
complicating healing.
Surgical Procedure:
After making the appropriate incision, the mucosal flap is elevated
to expose the underlying bone.
The torus is then carefully removed using appropriate surgical
instruments, ensuring minimal trauma to surrounding tissues.
Hemostasis is achieved, and the mucosal flap is repositioned and
sutured back into place.
Postoperative Care:
Patients may experience discomfort and swelling following the
procedure, which can be managed with analgesics.
Instructions for oral hygiene and dietary modifications may be
provided to promote healing and prevent complications.
Follow-Up:
Regular follow-up appointments are necessary to monitor healing and
assess for any potential complications, such as infection or delayed
healing.