hypertrophic cardiomyopathy (HCM)

its also called Asymmetric Septal Hypertrophy and also some books called it Idiopathic Hypertrophic Subaortic stenosis.

so from the name its characterized by hypertrophy specially if the left ventricle, the ventricle wall becomes thick, stiff, and thick, stiff and solid, and for this reason there will be forceful contraction that rapidly expel or push the blood, but there will be problems in diastole, there will be abnormal diastolic filling, there is no relaxation in the ventricle , the blood in the ventricle is greatly reduced, the so the ejection or expelling from the ventricle is ineffective (amount expelled is low), is in general what we see is decrease in cardiac output.

Pathogenesis: 

 studies said that 50% of HCM cases is inherited autosomal dominant trait and usually occurred by either:

• mutation in gene that synthesize the proteins such as beta-myosin heavy chain which occurs in about 30% of cases. \
• troponin I and T, alpha-tropomyosin and myosin ligh chains. 
• allelic heterogeneity which mean that genotype is caused by different mechanism.

pathology: 
 because of the hypertrophy, the heart become big and will wiegh more than 800gm. we see hypertrophy in the left ventricle and inter-ventricular spetum without dilation, the dilation may occur in the left atrium.

thickening in the walls of the ventricle will not be the same, for that reason it will be called Asymmetric septal hypertrophy.

Metabolism of cardiac muscle

now if we look at the cardiac muscle what is the big difference between the cardiac muscle and skeletal muscle???
 there are many difference, but basically the same metabolism takes place in the skeletal muscle and cardiac muscle except for few points.

functionally cardiac muscle is always working but skeletal muscle work and rest, so the cardiac muscle has a continuous job which requires continuous supply of energy for the contractivity. this is one of the major difference between skeletal muscle and cardiac muscle.

how muscle gets energy???
by the metabolism pathway:

1) glycolysis:
            the major substance here is glucose, glucose is the major fule that require for energy production. (note that glycolysis can be aerobic and anerobic)

so glucose molecule should be delivered in the cell which require insulin.

2) beta-oxidation of fatty acids:
 
3) glycolysis produce lactic acid (lactate)
lactate is utilized through conversion to glucose, its produced by anaerobic glycolysis and kori cycle.
 kori cycle is the conversion of glucose to pyrovate by lacated dehydrogenase enzyem then pyrovate is broken into Acytel CO which could be utalised in the TCA cycle for energy production.

now we compare the heart muscle to skeletal muscle they are the same except for few difference

the heart muscle is always pumping blood, as we say, the skeletal muscle is rapid or sustained movement, during movement it require energy, major pathway naturally aerobic pathway beta-oxidation and TCA cycle.

Beta-oxidation and TCA cycle require presence of oxygen so there are aeirobic pathway.

the aerobic pathway the same in the skeletal muscle as in cardiac muscle.

the main substrates is:
1) free fatty acids.
2) lactate
3) ketone bodies
4) VLDL
5)chylomicron

alpha receptor

There are 2 alpha receptor:

• alpha 1 receptor 
• alpha 2 receptor

Alpha 2 receptor: 

• presynaptic receptors 
• inhibitory receptors
• when stimulated; the end result will be inhibition of neurotransmition

Alpha 1 receptor:

• postsynaptic receptor
• stimulatory receptor
• stimulation will lead to stimulation; if in the blood vessels may lead to vasoconstriction

pharmacology: Spasmolytic drug

Spasmolytic drug: 

These drugs reduce abnormally elevated muscle tone that's spasm; without paralysis; without complete muscle paralysis relaxation, without loss strength of muscle

Spasmolytic agent don't ressemble Ach in the structure while both are competitive blocker.

All spasmolytic drugs are used orally; because these are highly potent compounds and unabsorbable when they are taken orally.

Spasmolytic don't act on neuromuscalar junction itself; but they are acting either:

• centrally on CNS 
• directly on muscle fiber

Drug acting on CNS centrally and spinal cord:

Diazepam:

• still used as sedative or hypnotic and some times as anticonvulsive effect
• its main effect is facilitated GABA amino gluetric acid mediated transmition 

Tizandine:

• act on spinal cord mainly
• clonidin like in their structure; used as anihypertensive 
• said to be an alpha 2 agonist

Drug acting on the muscle fiber:

Dantolene:

• act directly on the muscle fibe
• preventing Ca release from these muscle fiber; reducing the contraction or muscle tone.

pharmacology: Neuromuscular blockers

Neuromuscular blockers:

Drugs which can cause complete muscular paralysis or relaxation. there are 2 groups:

1. Competitive: characterized by long duration effects 
2. depolarizing neuromuscular: have short duration of effect.

 note: therapeutic use of these group of drug depends on the duraction of surgical procedure which we need muscular relaxation to perform. so for long duration like intraabdominal operation we will use competitive type; while for short procedure like Endotracheal intubation or electronconvulsive therapy we will use the depolarizing one (e.g., succinylicholine or suxamethonium)

note: depolarizing neuromuscular blocking agents usually given by IV infusion; because of their short duration effect.

note: after given of succinylcholine; at the beginning there will be muscular contraction; then after exhaustion of the muscle there will be relaxation.

adverse effects:

• bradycardia
• increase intraocular pressure 
• prolonged paralysis 
• malignant hyperthermia

bradycardia:
succinylcholine has muscurinic agonist activity similar to acetycholine; meaning that it can produce arrhythmia; and this might due to increase in plasma potassium level (hyperkalemia); that's why succinylcholine should be avoided in patient with severe muscular damage or tramua; becasue in these condition the plasma (blood) potassium is elevated.

Increase intraocular pressure:
succinylcholine may lead to increase introcular pressure; so its better not to use it in operation of eyeball; because it will lread to extravasation of intraocular fluid due increase in pressure

Prolonged paralysis:
these cases has been reported after treatment with succinlycholine; but only in patient with specific cases:

• patients who are genetically predisposed to have choline esterase deficiency (hypocholine esterasemia); so if there is a decrease in this enzyme (meaning choline esterase); the succinylcholine will stay for longed period in plasma or tissue; giving along duration of effect; prolonged paralysis 
• patients who receives anticholine esterase drugs 
• neonates and patients with their live disease; might have prolonged apnea; because in these group of patient there is inefficient metabolism of succinylecholine. 

Malignant hyperthermia: 
when used in patient who are receiving halogenated hydrocarbon for their general anethesia; some of theme may develop malignant hyperthermia

Chemotherapy

Chemotherapy:
its a term used for the drug treatment of parasitic infections (bacteria, portozoa, viruses, fungi, and helminthes); in which these parasites are destroyed by the drug, but without injury on the host.

Classification: 
 (A) According to causative agents:

1. antibacterial 
2. antifunal
3. antiviral
4. antiprotozoal
5. antihelmentics 

in turn; antibacterial could be classified by their action:

• Bacteriostatics: which inhibit bacterial growth
• bactericidal: kill the bacteria

important note: depending on the dose; the drug could be converted from bacteriostatics to bactericidal; meaning that at high dose at high dose they are converted to bactericidal and in low dose or normal dose they are bacteriostatics.

(B) According to the spectrum of activity: 

1. narrow spectrum
2. extended spectrum 
3. broad spectrum 

General Principles of chemotherapy: 

1. making the diagnosis:  means to know exactly the type of infection, the organism responsible for that & sensitivity testing.
2. removal of the barrier: make it easy for the drug to penetrate and to go to site of infaction
3. decide whether chemotherapy is really necessary: 
4. select the best drug: meaning that the drug should be very specific to the infection; keeping in mined the condition of the immune system of the patient; pregnancy & lactating 
5. the cost: the drug should be very effective and do not cost very much
6. optimum dose and frequency: this done by knowing the pharmacokientics of the drug

Important Problem we could face by using antibiotics:

1. drug resistence 
2. super infection
3. drug-drug interaction
4. adverse effect 

why knowing anatomy is important in microbiology ?

Knowing the anatomy is important because it will: 

1. how the infectious organism invade and infect the CNS 
2. how infection is going to take place  
3. sing and symptoms (S & S) that could be associated with the infection 
4. forming the diagnosis