Cancer

CANCER [MALIGNANT NEOPLASM]

Cancer is defined as any uncontrolled and unco-ordinated proliferation of cells
which invades the local tissue and metastasizes to distant organs.

The solid mass of uncontrolled cell growth is known as TUMOR.

TUMOR are of two types:

1.Benign tumors:
These are slow growing mass of neoplasm cells[cancer cells are known as neoplasm], which compresses the surrounding tissue(giving capsulated appearance) but never metastasizes to distant organs.[metastasis means lodgement or spread of neoplasmic cells to the nearby and distant organs, organs other than the origin of the tumor cells].They have good prognosis.The neoplasmic cells resemble the cells of the parent organ.As the proliferation of the cells occur by mitosis, benign tumors have fewer mitotic figures than the malignanat tumors.

2.Malignant tumors[cancer]:
These grow rapidly[NOTE: the proliferation of malignat tumor cells never exceeds than that of embryo, bone marrow or the intestinal epithelial cells], invade the surrounding tissues[grow into the surrounding tissue and deatroy them] and metastasizes to distant organs[lymph and blood are the route of metastasis, lymph being the most common route of metastasis].They usually have bad prognosis[prognosis:probability of cure and/or survival].The cells have more mitotic figures than the benign neoplasm.The cells of malignant tumor are morphologically and functionally different from the normal cells and the tumor cells are less organized than the cells of the parent organ.


Thus cancer and malignant tumor are synonyms. Its like cancer is the disease and they produce malignant tumor.Most cancer produce tumor but some like, leukemia don’t produce tumor.

The three characteristics of cancer:

1. they grow rapidly
2. they invade the surrounding tissues
3. they spread to the nearby and distant organs by help of blood or lymph, i.e. they metastasize.

Study of cancer is known as oncology.

CAUSES OF CANCER

Nearly all cancers have a genetic cause[ cancers are also known as clonal overgrowths], the proliferation is trigerred by ONCOGENES [oncogenes: genes causing cancer].Oncogenes are the activated form of proto-oncogenes i.e., proto-oncogenes are the normal version of the genes which when activated form oncogenes.Normally there are an another set of genes known as TUMOR-SUPRESSOR GENES. These prevent the cancers.When tumor-supressor genes are inactivated and proto-oncogenes activated [to form oncogenes] cancer results.


1.CARCINOGENES: THE substances or the agents causing cancer are known as carcinogens. Aflatoxins produced by Aspergillus , tobacco[tar of cigarette] ,betel nut(causes oral cancer) , smoke, , high energy radiations ( gamma rays, x-ray, uv ray and alpha particles), chemicals (benzopyrines, inhaled asbestos, cadmium, nickel ,vinyl chloride, nitrosamine, benzene etc,) , infectious agents/biological agents/pathogenes ( such as certain viruses like HPV [ human papilloma virus cause cervical cancer ], hepatitis B and hepatitis C virus causes liver cancer, Rous sarcoma virus , Epistein-barr virus and bacteria Helicobacter pylori [causes stomach cancer]).


2.HORMONAL DISBALANCE:Increased level of estrogen is associated with endometrial cancer.

3.IMMUNE-SYSTEM DYSFUNCTION:In immuneocompromised patients like in case of AIDS, a lot of malignancies are associated like Kaposis’ sarcoma and non-Hodgkin’s lymphoma.

4.HEREDITARY CAUSES:Most forms of cancer have no hereditary cause and are sporadic. However some cancers have hereditary associations.

5.AGE: The risk for cancer increases with the age.

6.ETHNICITY/ RACE:Gastric cancer is more common in Japan and Colon cancer is more common in the United States.

7.SEX

8.DIETARY HABBITS:Alcohol consumption is associated with oral and esophageal cancer.Grilled meat increases the risk of stomach cancer.

9.LIFESTYLE

[Age, sex, ethnicity, lifestyle, and dietary habbits are considered as risk factors for cancer.]


CLASSIFICATION OF CANCER

On the basis of the origin cancer is classified as:

1.CARCINOMA: Malignant tumors derived from the epithelial cells.For eg: Breast (carcinoma of breast). Liver (hepatocellular carcinoma), carcinoma of lung, carcinoma of stomach, carcinoma of colon, squamous cell carcinoma, renal cell carcinoma, carcinoma of prostrate, melanoma, seminoma [note: usually for naming benign tumor “-oma ‘suffia is added for example:lipoma is the benign tumor of fat cells, but melanoma( melanocytes), seminoma(seminiferous tubules) and thymoma (thymus) are some malignant neoplasms] thymoma, endometriod carcinoma etc. Carcinoma In Situ is the pre-malignant condition where the signs of malignancy is present but there is no evidence of invasion.i.e, CIS may transform to carcinoma.



2.SARCOMA: Malignant tumors derived from the connective tissues ( bone, cartilage, fat, muscle, blood vessles etc) Examples include: bone(osteosarcoma), cartilage(chondrosarcoma), smooth muscle(leiomyosarcoma), skeletal muscle (rhabdomyosarcoma), fat (liposarcoma) [note: liposarcoma is malignant tumor, but lipoma is benign tumor, ie usually “oma”suffix is added for naming benign tumor and “-osarcoma ia added for naming malignant tumor of connective tissue origin] , blood vessles(hemangiosarcoma), lymph vessles(lymphangiosarcoma).

3.CANCER DERIVED FROM BLOOD FORMING CELLS[HEMATOPOITIC CELLS]

LEUKAEMIA: cancer of blood or bone marrow especially that of WHITE BLOOD CELLS.

LYMPHOMA: cancer of lymphocytes . Lymphomas often originate in lymph nodes.

MULTIPLE MYELOMA: cancer of plasma cells

4.GERM CELL TUMORS:TUMORS DERIVED FROM TOTIPOTENT CELLS. Benign tumors are known as “mature teratoma” while malignant tumors are known as “immature teratoma” or “dysgerminoma”

5.BLASTIC TUMORS: Blastic tumors represent the malignant tumors resembling the immature or embryonic tissue.These are mostly common in the child hood. For eg: RETINOBLASTOMA, NEUROBLASTOMA etc.

$ The commonest cancer in childhood is ALL(Acute lymphocytic leukemia)
$The commonest cancer in the males is stomach cancer(in the world)
And lung cancer in Nepal.
$ The commenest cancer in females is breast cancer (in the world)
And cervical cancer in Nepal.


CLINICAL SIGNS OF CANCER

*local swelling, lumps, hemorrhage, pain, ulceration etc are the local signs.
*signs of metastasis: enlarged lymph nodes, hemoptysis etc.
*systemic symptoms:poor appetite, weight loss, fatigue, cachexia(wasting), night sweats, anaemia etc.

DIAGNOSIS
Cancer is diagnosed with the help of BIOPSY{REMOVAL OF THE TISSUE FOR EXAMINATION}, FNAC{FINE NEEDLE ASPIRATION CYTOLOGY}:STUDY OF CELLS..[NOTE: CERVICAL CARCINOMA IS DIAGNOSED BY PAP SMEAR-PAPALICOLAU SMEAR]

TREATMENT
1.SURGICAL EXCISION
2.RADIATION THERAPY(RADIOTHERAPY)
3.CHEMOTHERAPY/ANTI CANCER DRUGS: methotrexate, flurouracil, cisplatin etc.

The Integumentary System

INTEGUMENTARY SYATEM

[skin + derivatives = integument ]

$SKIN IS THE LARGEST ORGAN OF THE BODY/LIVER IS THE LARGEST GLAND.[JACK OF ALL TRADES== SKIN]


SKIN= EPIDERMIS [outer] + DERMIS [inner]


EPIDERMIS is ectodermal in origin.[$$ BLOOD VESSELS ABSENT IN THE EPIDERMIS]
DERMIS is mesodermal in origin.


EPIDERMIS is composed of stratified squamous epithelium, and consists of 5 layers.

1.STRATUM CORNEUM =[[$$ str. Corneum of frog contains living non-nucleated flattened cells][=è metachoresis change in skin colour in frog]] outermost layer of dead keratinized cells [keratin is a scleroprotein]. It is **thick at sole and palm. Ecdysis is shedding of stratum corneum.

2.STRATUM LUCIDUM =A thin translucent layer of dying keratinized cells which contain eleidin .*Conspicuous in soles and palms.

3.STRATUM GRANULOSUM = 2 – 4 cells deep layer, containing$ keratohyalin, conspicuous in palm and soles.

4.STRATUM SPINOSUM = CELLS ARE POLYHEDRAL

5.STRATUM BASALE = lowermost layer of columnar epithelium cells which rest on a basement membrane.divide by mitosis to form outer cells.all the keratinized structures and glands are derived from this layer.

[$$stratum spinosum + stratum basale = STRATUM GERMINATIVUM/ malpighii]

DERMIS[CORIUM]

It is a thick sheet of connective tissue present below the epidermis.About 2- 3 times thicker than epidermis.CONNECTIVE TISSUE is areolar which is dense due to abundant fibers.Blood vessels, nerve fibres, glands , muscle fibres, sanse receptors and hair follicles are present in the dermis.
$$[SENSE RECEPTORS ARE DERMAL IN ORIGIN AND HAIR AND GLANDS ARE EPIDERMAL IN ORIGIN]

$ CHROMOPHIL CELLS / MELANOCYTES produce melanin.melanocyte are present/produced in dermis but get incorporated into epidermal cells.$ albino colour /albinism:due to non-synthesis of melanin from melanocytes.[$$$ melanin synthesis: tyrosinàdopaàdopaquinoneàmelanin]

DERMIS = PARS PAPILLARIS + PARS RETICULARIS
PARS PAPILLARIS [outer]= Includes papilla and connective tissue with blood capillaries.
PARS RETICULARIS[inner] = INCLUDES lower thick connective tissue fibres with bigger blood vessels and nerves.

SENSE RECEPTORS^

1.FREE NERVE ENDINGS = SENSITIVE TO pain , touch, pressure.
2.BASKET NERVE ENDINGS / HAIR END ORGANS = TOUCH AND MOVEMENT OF OBJECTS.
3.RUFFINI’S CORPUSCLES = warmth receptors
4.KRAUSE’S END BULBS = cold sensation
5.MEISSNER’S CORPUSCLES = touch
6.PACINIAN CORPUSCLES = tissue vibrations and strong pressure
7.GOLGI-MAZZONI CORPUSCLES = heavy touch a\, pressure joint rotation
8.MERKEL’S CORPUSCLES = constant touch

[$$ VITAMIN D = Skin manufactures vit D from *cholesterol *]


GLANDS FOUND IN THE SKIN[$$ simple coiled tubular glands occur in the dermis of the skin]

1.SWEAT GLANDS = [sudoriferous glands] coiled tubular opening on the skin surface through a pore.secrets sweat [composition:H20, urea, NaCl,etc]

$SWEAT GLANDS ABSENT AT LIP TIPS IN MAN.$$ BUT IN RABBIT PRESENT ONLY ON LIPS, AND RARE ELSE WHERE.SWEAT HELPS IN LOWERING BODY TEMPERATURE]

2.OIL GLANDS/ SEBACEOUS GLANDS = flask shaped, alveolarglands opening into shaft of hair follicles and secrete oil for lubricating hair and skin.

3.lachrymal/lacrimal glands = OCCURS IN THE EYES, secrete tears

4.meibomian glands: SEBACEOUS GLANDS OPENING IN THE EYE LASHES.[ TARSAL
GLANDS/ PALPEBRAL GLANDS]

5.WAX / CERUMINOUS GLANDS = MODIFIED SWEAT GLANDS

6.MAMMARY GLANDS/MILK GLANDS = MODIFIED LOBULATED SWEAT GLANDS

7.SCENT GLANDS = MODIFIED SEBACEOUS GLANDS WHICH SECRETE $$PHEROMONES $$.========è


APPENDAGES OF SKIN-àHAIR AND CLAWS, NAILS, HOOFS FOUND IN THE SKIN.


1.HAIR: A fine kertinised filaments that develop from tubular pits known as hair follicles.Hair papilla present at the lower end of hair follicle is composed of connective tissues and nerve fibres.
Arrector pilli muscles[smooth / involuntary] are for movement of hair, $ GOOSE FLESH=èDUE TO CONTRACTION OF THESE MUSCLES IN COLD]
Bulb/root of the hair introduces new cells.
Besides bulb hair has root[inside skin] and shaf [outside skin]


2.CLAWS, NAILS, HOOFS = These are the keratinized epidermal structures developing from tips of digit.



FUNCTIONS OF THE SKIN

1.streatchable protective shield.
2.regulation of body temperature
3.sense reception
4.screen UV rays
5.synthesis of vit D
6.excretion of waste materials.


$ Body temperature is regulated by : [IOM 1995]=èskin, mouth, lungs
$The loss of heat in a spector inside cinema hall is mainly through [IOM 1995]èCONVECTION
$All of the following structures are found in the dermis except [IOM 1993]è
a.blood vessles c.sweat glands
b.sebaceous glands d.melanocytes
[ans:c]

The circulatory system - The Heart.

Circulatory system

[heart]


# Circulatory system was discovered by Aristotle.

# Closed type of circulatory syatem [blood-vascular system] was discovered by William Harvey.


Protists, porifers, coelenterates etc have a large surface area to volume ratio, so, diffusion or cytoplasmic streaming(cyclosis) is sufficient for exchange of materials between the organisms and the surrounding.
In the multicellular organisms, a specific circulatory system is needed to transport nutrients, gases, wastes, hormones etc. A typical circulatory system has 3 distinct features –
i) a circulating fluid [blood, lymph]
ii) a pumping organ [heart- human heart acts as a compression pump ]
iii)asystem op tubes through which the circulating fluid move.


TYPES OF CIRCULATORY SYSTEM

There are two types – open circulatory system and closed circulatory system.

1.Open type of circulatory system:
In open circulatory system the blood not only flows through the blood vessels but also through open spaces called lacunae and sinuses.The flow is slow and under low pressure and it is less efficient then closed type of circulatory system.this type of circulation is present in arthropods, most molluscs.

2.Closed type of circulatory system:
Blood flows in vessles only and it doesn’t come in direct contact with the tissue.The exchange of materials is mediated by INTERSTITIAL FLUID.The flow is fast and under high pressure.This type of circulation is more efficient to exchange materials as the flow is fast.Present in most annelids, cephalopods, all vertebrates, echinoderms.



Mammalian heart

The heart is a conical, muscular, hollow, mesodermal organ lying in the thorax above the diaphragm between the lungs in the middle mediastinum towards the left of the body with broad base upwards and pointed apex facing downwards.
Size of human heart: 12 cm by 9 cm by 6cm
Weight:300 gm in male, 250 gram in female.
Capacity : about 120 ml.
COVERINGS OF THE HEART:Heart is covered by a fibroserous covering known as pericardium.PERICARDIUM is composed of two layers –

1.outerfibrous layer , the fibrous pericardium, which is continuous with the tunica externa/adventitia of the blood vessles entering and leaving the heart.It prevents excessive distention of the heart.

2.inner serous layer, the serous pericardium.It is composed of two layers –the outer PARIETAL LAYER and the inner VISCERAL LAYER. The parietal pericardium is continuous with the parietal covering of the thorax .the visceral paericardium is continuous with the visceral layer of the thorax.Visceral pericardium is also known as EPICARDIUM. In between these two layers of serous pericardium is present PERICARDIAL FLUID, about 60 ml. It protects the heart from friction, mechanical shock, and external injury.

THE WALL OF THE HEART

The heart wall is composed of three layers
i) PERICARDIUM
ii) MYOCARDIUM: It is made of cardiac muscle.Cardiac muscle is involuntary musle.It has faint but regular cross-striations.It occurs as a network pattern called the syncytium.It is usually UNINUCLEATE [but sometimes binucleate].There is presence of INTERCALATED DISCS, large number of mitochondria, abundant blood supply. Contraction of these muscles help heart pump the blood..The heart starts to beat in 4th week of intra-uterine life[28 days of featal life], and continuously beat in rhythmic pattern throughout the life.THUS HEART IS SAID TO BE THE BUSIEST ORGAN OF THE BODY.The cardiac myocytes contract rhythmically and continuously.The ions required for contraction of cardiac myocytes are Na, K, and Ca.The Energy required is derived from carbohydrates (35%), aminoacids(5%), and fatty acids(60%).Automaticity/autorhythmicity, conductivity, frank-starling law[heart pumps all the blood it receives], resting membrane potential [ responsible for automaticity of cardiac muscles] of the cardiac myocytes is about -85 to -95 mV.
iii) ENDOCARDIUM: It consists of the flat epithelial cells.this layer is continuous with the endothelium of the blood vessels entering and leaving the heart.



THE HEART CONSISTS OF 4 CHAMBERS : 2 ATRIA AND 2 VENTRICLES.
THE ATRIA ARE SEPARATED FROM THE VENTRICLES BY ANNULAR PAD INTERNALLY AND EXTERNALLY THERE IS PRESENCE OF A CORANARY SULCUS.
$ THE RIGHT ATRIUM AND VENTRICLE IS ALSO KNOWN AS THE PULMONARY/VENOUS HEART.
$THE LEFT ATRIUM AND VENTRICLE IS ALSO KNOWN AS THE SYSTEMIC/ARTERIAL HEART.

THUS MAMMALIAN CIRCULATION IS CALLED AS DOUBLE CIRCULATION. DOUBLE CIRCULATION IS MORE EFFICIENT THAN TH E SINGLE CIRCULATION FOUND IN THE FISHES[ HEART OF FISHES ONLY GETS VENOUS BLOOD, HEART OF PRAWN ONLY GETS ARTERIAL BLOOD]


1.ATRIA: ATRIA gets blood from different parts of the body.The right atrium gets deoxygenated blood from all over the body and the left atrium gets oxygenated blood from the lungs.The right and left atria are separated by INTER-ATRIAL SEPTUM.There is presence of FOSSA OVALIS, which is the remnant of the FORAMEN OVALE present in the featal heart.

A) THE RIGHT ATRIUM:It gets deoxygenated blood from all over the body. The blood is carried by superior vancava and inferior vanacava. Venacava is the largest vein in the body. There is presence of EUSTACHIAN VALVE at th eopening of the inferior venacava. Superior venacava is devoid of valve[ other vein without valves are internal jugular vein, pulmonary vein and brain sinuses]. Each atrium is produced behind into a swollen flap called auricular appendage.Low muscular ridges present in the right atrium are kniwn as the MUSCULI PECTINATI/PECTINI..In the mammalian heart sinus venosus is absent.The remnant of sinus venosus is represented by SA NODE(THE PACEMAKER OF HEART). There is also an opening of CORONARY SINUS in the right atrium.(Coronary sinus drains blood from the wall of the heart), the opening of coronary sinus is guarded by,THEBESISAN VALVE.In case of rabbit there are two precaval veins(superior vanacava) and one postcaval vein(inferior venacava)
B) THE LEFT ATRIUM: It gets oxygenated blood from the lungs through 4 pulmonary veins[ the other vein carrying oxygenated blood is UMBLICAL VEIN].In casse of rabbit there are only two pulmonary veins


The right atrium communicates with the left ventricle through the tricuspid valve(as it has three cusps) ant the left atrium communicates with the left ventricle by bicuspid valve/ mitral valve(as it has 2 cucsps)These valves prevent the regurgitation of the blood back to the aria.


2.VENTRICLES:Ventricle get blood from the atrium and pumps it to other parts of the body.The right ventricle pumps to the lungs through th pulmonary trunk and the left ventricle pumps to different parts of the body.The left ventricle is at least 3 times thicker than the right ventricle.The valves between the atria and ventricles are jopined to the muscles of ventricles by chordae tendinae[cords like structures] to special muscles known as papillary muscles(conical projections).TRUNCUS ARTERIOSUS AND CONUS ARTERIOSUS ARE ABSENT IN MAMMALIAN HEART.BUT PRESENT IN HEART OF THE FROG.[FROG HAS 3 CHAMBERS- 2 ATRIA AND 1 VENTRI CLE, AND IT HAS 2 ACSSECORY CHAMBERS, CONUS ARTERIOSUS AND SINUS VENISUS]

The right ventricle pumps blood to the pulmonary artey(artey carrying impure blood), the opening of the pulmonary artey is guarded by semilunar valves(3 in number).The left ventricle pumps blood to the aorta, the opening of which is guarded by semilunar valves(3 in number)



BLOOD SUPPLY OF THE HEART: CORONARY ARTERY [first branch of aorta] supplies the oxygenated blood to the heart.CORONARY SINUS and THEBESISAN VEINS drain deoxygenated blood from the heart to the right atrium.
NERVE SUPPLY OF THE HEART: PARASYMPATHETIC SUPPLY by VAGUS NERVE.
SYMPATHETIC SUPPLY by CARDIAC NERVE PLEXUS.

CONDUCTION SYSTEM OF THE HEART:The cardiac myocytes are said to be myogenic and the mammalian heart is a myogenic heart i.e. the heart beating originates in the specializedcardiacmyocytes:the SA Node, interatrial fibres, AV Node, Bundle of his/AV Bundle, Left and Right Bundle branch and Purkinje fibres are the components of conductionsystem of heart.
SA Node is said to be the pacemaker of the heart as the heart beat originates from it. It has got highest autorhythmicity [72-80/min] but lowest conductivity [0.05m/sec]. It is situated near the opening of the superior venacava, and it is remnant of sinus venosus.
Inter-atrial fibres:These fibres carry impulses to the left atrium, so that both the atria contract together.
AV Node:It is situated at the interatrial septum near the tricuspid valve.It is said to be the PACESETTER, as it conducts impulse from atria to the ventricles.
AV Bundle/Bundle of His:It lies below the AV node and is it’s continuation.It divides to give Right and Left bundle branche.The Right bundle branch supplies the right ventricle, and the left bundle branch supplies the left ventricle.The fine branches of these which supply the ventricular wall are called the PURKINJE FIBRES, they have lowest automaticity[15-45/min] but highest conduction velocity[4m/s].BOTH THE VENTRICLES CONTRACT TOGETHER.
CARDIAC OUTPUT: It is the blood pumped by each ventricle in one minute.[The blood pumped by each ventricle in one beat is called stroke volume.it is about 70 ml]. Cardiac output is about 5L.
Cardiac Output = Stroke Volume * heart rate
=70 ml * 72 /minute
=5400 ml/min.

Cardiac output is measured by using Fick’s Principle.

Heartrate in an adult is 72 bpm(beats per minute)..The normal range is 60 – 100 bpm. Below 60 bpm is called as bradycardia and above 100 bpm is called as tachycardia.
Heartrate in fetus:140-160 bpm
Newborns:120 -140 bpm
Children:80 – 120 bpm
Heart rate is controlled by the cardiac centre in the Medulla.
HeartRate is measured clinically as pulse in the Radial artery at the wrist joint.

HeartRate Is Increased in Inspiration, Excitement, fever [ but bradycardia in Typhoid fever], exercise etc and it is decreased during expiration, fear, grief etc.


The Cardiac output Received by different organs:
Liver :25%(maximum)
Kidney:maximum CO per gram tissue weight per minute.(25%)
Brain: 25% heart:5%
20%:remaining organs


CARDIAC CYCLE:The series of electrical and mechanical events that occur in the heart in one beat. The total duration of one cardiac cycle is 0.8s.
Heartbeat has two phases : contraction phase(systole) and relaxation phase(diastole)
Atrial systole:0.1 s
Atrial diastole:0.7 s
Ventricular systole:0.3s
Ventricular diastole:0.5s