The Gallbladder and bile ducts

Gallbladder

• The gallbladder is a pear-shaped reservoir in continuity with the common hepatic and common bile ducts through the cystic duct.
•  It is usually 7.5 to 12cm in length, is 3 to 5 cm in diameter, and has a capacity of 35 to 50 mL.
•  The gallbladder lies on the inferior surface of the liver partially enveloped in a layer of peritoneum.
•  The gallbladder is anatomically divided into the fundus, body, infundibulum, and neck, which empties into the cystic duct.
•  Both the gallbladder neck and the cystic duct contain spirally oriented mucosal folds known as the valves of Heister. 
• The valves prevent the passage of gallstones and excessive distention or collapse of the cystic duct, despite variations in ductal pressure. 

The Hepatic Duct (ductus hepaticus)

• Two main trunks of nearly equal size. Arising from the liver at the porta. one from the right, the other from the left lobe.
• The common hepatic duct is less than 2.5cm long  and is formed by the union of the right  and left hepatic ducts.
• It passes downward and to the right for about 4 cm.
• Joined at an acute angle by the cystic duct to form the common bile duct. Lies between  the layers of the lesser omentum.
• Is accompanied by the hepatic artery and portal vein. 

Cystic duct

The cystic duct varies in length from 1 to 5 cm and in diameter from 1 to 3 mm; it usually joins the common hepatic duct at an acute angle.

The Common Bile Duct 

The common bile duct is formed by the junction of the cystic and hepatic ducts.

• Length: It is about 7.5 cm. long.
• Diameter: That of a  goose-quill.

• Course and extent : It descends along the right free margin  of the lesser omentum along with   portal vein ( which is behind it ) , and to the right of the hepatic artery. 
• Then behind the superior portion of the duodenum,
• After crossing the duodenum, it runs on the posterior surface of the head of the pancreas, and in front of IVC. 
• Occasionally completely imbedded in the pancreatic substance. 
• At its termination it lies for a short distance along the right side of the terminal part of the pancreatic duct and passes with it obliquely between the mucous and muscular coats. 
• The two ducts unite and open by a common orifice upon the summit of the duodenal papilla, situated at the medial side of the descending portion of the duodenum, a little below its middle and about 7 to 10 cm. from the pylorus. The short tube formed by the union of the two ducts is dilated into an ampulla, the ampulla of Vater. 

Blood supply

• Gall bladder is supplied by Cystic artery, a branch of right hepatic artery.
• The blood supply to the common hepatic duct, cystic duct and common bile duct comes from the gastroduodenal, retroduodenal, postero-superior pacreatico duodenal arteries. 

Lymphatics

• The lymphatics of gallbladder (subserosal and submucosal) drain into the cystic L/N of Lund.
• Small veins and lymphatics course between the gallbladder fossa and the gallbladder wall, connecting the lymphatic and venous drainage of the liver and gallbladder. These connections are the cause of the direct inflammatory and carcinomatous spread from the gallbladder into the liver.

Calot’s triangle

Formed by:

• Common hepatic duct to the left
• Cystic duct below and 
• inferior surface of the liver above.

Content:

• the cystic artery, 
• the right hepatic artery, and
• the cystic duct lymph node.

Functions of gall bladder

• Stores bile
• Concentrates bile
• Secretion of mucus

Embryology

• The hepatic diverticulum arises from the ventral wall of the foregut and elongates into a stalk to form the choledochous.
• A lateral bud is given off, which becomes the gall bladder and the cystic duct.

Congenital abnormalities

• Absence of the gall bladder
• The Phrygian cap
• Floating gall bladder
• Double gall bladder
• Absence of the cystic duct
• Low insertion of the cystic duct
• An accessory cholecystohepatic duct

Biliary atresia

It may be due to viral infection or defective embryogenesis resulting in the inflammatory destruction of extra- and intrahepatic biliary tree.
Incidence 1 in 12000 live births
Male and female equally affected.
It may be associated with: cardiac lesions, polysplenia, situs inversus, absent vena cava and a preduodenal portal vein.

Classification

Type I: atresia restricted to the common bile duct
Type II: atresia of the common hepatic duct
Type III: atresia of the right and left hepatic ducts

Clinical features

• Progressive jaundice in a new born.
• Steatorrhea
• Osteomalacia
• Biliary rickets
• Severe pruritus
• Clubbing and skin xanthomas

D/D

• Alpha 1-AT deficiency
• Cholestasis associated with i.v feeding
• Choledochal cyst
• Inspissated bile syndrome
• Neonatal hepatitis

Treatment
In correctable cases:
Roux-en-Y hepaticojejunostomy
In noncorrectable cases:
Hepaticoportojejunostomy (Kasai’s operation)
Radical excision of all bile duct tissue up to the liver capsule is performed.
A roux-en-Y loop of jejunum is anastomosed to the exposed area of liver capsule above the bifurcation of the portal vein creating a portoenterostomy

Liver transplantation: in case of unsuccessful

Caroli’s disease

It is a congenital, multiple, irregular dilatations of the intrahepatic ducts with stenotic segments in between.
Extrahepatic biliary system is normal.

Types :

Simple type
Presents later with episodes of aqbdominal pain and biliary sepsis

Associated with:
Congenital hepatic fibrosis
Polycystic liver
Cholangiocarcinoma
Periportal fibrotic type
Presents in childhood

Periportal fibrotic type is associated with:
Biliary stasis
Stone formation and
Cholangitis

T/T

• Antibiotics for chalangitis and removal of calculi.
• If limited to one lobe of liver- lobectomy

Choledochal cyst

Choledochal cysts are congenital dilations of the intra- and/or extrahepatic biliary system.

Classification (Todani)

Type Ia and b: diffuse cystic
Type II: diverticulum of the common bile duct
Type III: diverticulum within the pancreas
Type IV: extension into the liver
Type V: cystic dilatation only of the intrahepatic ducts

Clinical features

• Can occur in any age.
• Patients may present with jaundice, fever, abdominal pain.
• O/E right upper quadrant mass which is smooth, soft, not moving with respiration, not mobile and resonant.

Ix

Ultrasonography abdomen:
Confirms the presence of  abnormal cyst

MRI/MRCP:  
reveals anatomy. Esp. relationship between the lower end of the bile duct and the pancreatic duct.

CT: 
show the extent of intra- and extrahepatic dilatation.

Treatment
Radical excision of the cyst is the t/t of choice with reconstruction of the biliary tree using a RouX-en-Y loop of jejunum.

Bilirubin metabolism

High & Low frequency sounds

Low frequency sound is best detected at the apex of the cochlea near the helicotrema. High frequency sound is best detected at the base of the cochlea near the oval and round windows

The Thalamus as its ''Relay'' function

the thalamus is a part of diencephalon and has multiple functions. It translates information from all sensory pathways other than Olfaction and selectively distributes those impulses to appropriate parts of the cortex (''relay'' function). The following thalamic nuclei receive input from sensory pathways:

1.Ventral posterolateral (VPL) receives input from the spinothalamic tract (pain and temperature sensation) and medial lemniscus(position and proprioception). It transmits impulses to primary somatosensory cortex (Brodmann areas 3,1 & 2).
2.Ventral posteromedial nucleus (VPM) receives inputs from the trigeminal and gustatory pathways and transmits them to the primary sensory cortex (Brodmann's areas 3, 1 & 2).
3.Lateral geniculate body is a ''relay'' nucleus for the vision pathway. It receives impulses from the optic nerve and transmits them via the optic radiations to the visual cortex (calcarine sulcus)
4.Medial geniculate body is a part of the auditory pathway. It receives impulses from the superior olivary nucleus and the inferior colliculus of the pons, and projects them to the auditory cortex of the temporal lobe (Brodmann areas 41 & 42)

The olfactory tract is the only sensory pathway where input is not processed through thalamus.

Cerebrospinal tracts

Extraocular Muscles : Function and Innervation

Eye Movement Control Systems

Extraocular Muscles : Function

Superior Oblique muscle : can depress and abduct the eye from the neutral position. From the adducted position, it is the only muscle that can depress the eye

Inferior Oblique muscle : can elevate and abduct the eye from the neutral position.From the adducted position, it is the only muscle that can elevate the eye

Superior rectus muscle : can elevate and adduct the eye from neutral position. it is the only muscle that can elevate the eye from the abducted position

Inferior rectus muscle : can depress and adduct the eye from the neutral position. From the abducted position , it is the only muscle that can depress the eye.

The Lateral rectus muscle can abduct the eye.

Innervation:

Cranial Nerve III :

• Medial rectus : adducts eye
• Superior rectus : elevate, intorts, adducts eye
• Inferior rectus  : depresses, extorts, adducts eye
• Inferior Oblique: elevates, extorts, abducts eye

Cranial Nerve IV : 

• Superior Oblique : depresses, intorts , abducts eye

Cranial Nerve VI : 

• Lateral rectus: Abducts eye.

Intraperitoneal and Retroperitoneal Organs

Major Intraperitoneal Organs: (suspended by a mesentery)

• Stomach
• Liver and Gallbladder
• Spleen
• Duodenum, 1st part
• Tail of pancreas
• Jejunum
• Ileum
• Appendix
• Transverse colon
• Sigmoid colon

Major Secondary Retroperitoneal Organs : (loss of mesentery during development)

• Duodenum 2 & 3 parts
• Head ,neck, & body of pancreas
• Ascending colon
• Descending colon
• Upper rectum

Major Primary Retroperitoneal Organs : (never had a mesentery)

• Kidneys
• Adrenal glands
• Ureters
• Aorta
• Inferior vena cava
• Lower rectum 
• Anal canal

Germ layer Derivatives Ectoderm (Neural crest)

Neural crest

• Adrenal Medulla

• Ganglia :

-Sensory-pseudounipolar neurons
-Autonomic-postganglionic neurons

• Pigment cells

• Schwann cells

• Meninges- Pia and arachnoid mater

• Pharyngeal arch cartilage

• Odontoblasts

• Parafollicular (C) cells

• Aorticopulmonary septum

• Endocardial cushions 

CORONARY ARTERIES

From: Ascending aorta
To: Myocardium 

Right coronary artery. Originates from the anterior (new nomenclature: right) aortic sinus. It passes anteriorly between the pulmonary trunk and the right auricle to reach the atrioventricular sulcus in which it runs down the anterior surface of the right cardiac border and then onto the inferior surface of the heart. It terminates at the junction of the atrioventricular sulcus and the posterior interventricular groove by anastomosing with the circumflex branch of the left coronary artery and giving off the posterior interventricular (posterior descending) artery. It supplies the right atrium and part of the left atrium, the sinuatrial node in 60% of cases, the right ventricle, the posterior part of the inter- ventricular septum and the atrioventricular node in 80% of cases.
Left coronary artery. Arises from the left posterior (new nomenclature: left) aortic sinus. It passes laterally, posterior to the pulmonary trunk and anterior to the left auricle to reach the atrioventricular groove where it divides into an anterior interventricular (formally left anterior descending) artery and circumflex branches.
The circumflex artery runs in the atrio- ventricular sulcus around the left border of the heart to anastornose with the right coronary artery. The anterior inter-ventricular artery descends on the anterior surface of the heart in the anterior interventricular groove and around the apex of the heart into the posterior interven-
tricular groove where it anastomoses with the posterior interventricular branch of the right coronary artery. The left coronary artery supplies the left atrium, left ventricle, anterior interventricular septum, sinuatrial
node in 40% of cases and the atrioven- tricular node in 20%.
Dominance. In approximately 10% of hearts the posterior interventricular artery arises from the circumflex artery (left coronary) and then most of the left ventricle and interventricular septum are supplied by the
left coronary artery. The heart is said to have left cardiac dominance.

Important presentation about Thalassemia (Microcytic Anemia)

• Definition: hereditary underproduction of either the alpha or beta globin chains of the hemoglobin A  resulting in a  microcytic anemia.
• Beta thalassemias are due to mutations in the HBB gene on chromosome 11.
• The α thalassemias involve the genes HBA1 and HBA2 on chromosome 16.

Beta- Thalassemia

• The β-globin mutations associated with β-thalassemia fall into two categories: 
• (1) β0, in which no β-globin chains are produced; and 
• (2) β+, in which there is reduced (but detectable) β-globin synthesis
• Individuals inheriting one abnormal allele have thalassemia minor or thalassemia trait, which is asymptomatic or mildly symptomatic. 
• Most individuals inheriting any two β0 and β+ alleles have β-thalassemia major; 
• occasionally, individuals inheriting two β+ alleles have a milder disease termed β-thalassemia intermedia.

Alpha-Thalassemias

• alpha- thalassemias result in decreased alpha-globin production, therefore fewer alpha-globin chains are produced, resulting in an excess of β chains in adults and excess γ chains in newborns.The excess β chains form unstable tetramers (called Hemoglobin H or HbH of 4 beta chains) which have abnormal . The severity of the alpha- thalassemias is correlated with the number of affected alpha-globin genes.  
•  alpha0 thalassaemias, where there is lots of gama4 but no alpha-globins at all (referred to as Hb Barts), often result in still birth.

• The most severe form of alpha thalassemia major causes stillbirth.
• Other symptoms can include:
• Bone deformities in the face
• Fatigue
• Growth failure
• Shortness of breath
• splenomegaly

Diagnostic features of beta-thalassaemia

Dx

• A physical exam may reveal a swollen (enlarged) spleen.
• Blood test:
• Red blood cells will appear small and abnormally shaped when looked at under a microscope.
• A complete blood count (CBC) reveals anemia.
• A test called hemoglobin electrophoresis shows the presence of an abnormal form of hemoglobin

Rx

• Treatment for thalassemia major often involves regular blood transfusions and folate supplements.
• If you receive blood transfusions, you should not take iron supplements. Doing so can cause a high amount of iron to build up in the body, which can be harmful.
• Persons who receive significant numbers of blood transfusions need a treatment called chelation therapy to remove excess iron from the body.
• Bone marrow transplant may help treat the disease in some patients, especially children.
• Hydrops fetalis: none available 
• Haemoglobin H: no specific therapy required; avoid iron therapy; folic acid if necessary 

TREATMENT OF BETA-THALASSAEMIA MAJOR

REGULATION OF RESPIRATION

PONTO MEDULLARY RESPIRATORY CENTERS

ALL ARE PAIRED & INTERCONNECTED

RESPIRATORY CENTERS:-

PNEUMOTAXIC CENTER:

• Location: Upper Pons
• Absence causes APNEUSTIC BREATHING (Esp when the vagi are cut)
• Curtails inspiratory activity & thus can increase the rate of respiration

APNEUSTIC CENTER:

• Location: Lower Pons
• Stimulates the Inspiratory Center and increases Inspiration
• Gets feed back from Vagi & other Centers.

RESPIRATORY CONTROL ORGANIZATION:MODERN CONCEPT

• All the respiratory centers are termed as the BULBOPONTINE RESPIRATORY NEURONAL COMPLEX
• There is an inspiratory ramp generator called Respiratory Control Pattern Generator: Pre Bottzinger Complex
• The Inspiratory Off switch(IOS) is fine tuned by PTC & the chemoreceptor drive.
• Both Neural & Chemical controls are well coordinated.

PERIPHERAL INFLUENCES ON RESPIRATORY CONTROL

LUNG OR PULMONARY RECEPTORS:

• Receptors in and around the lungs.

CHEMORECEPTORS

• Peripheral Chemoreceptors
• Central Chemoreceptors.

PERIPHERAL INFLUENCES

• The four influences from the lungs are:
• Pulmonary stretch receptors
• Lung irritant receptors
• J receptors
• Proprioceptors
• Along with the chemoreceptors, these receptors send information to the respiratory centers.

HERING BREUER(HB) REFLEX

• It is a ‘Volume’ reflex.
• Receptors are located in between the smooth muscles of the small airways.
• These receptors are unmyelinated nerve endings.
• They are stimulated by the change of shape of the Airways.

• Excessive deflation of the lungs causes Inspiration.
• This reflex prevents Atelectasis.
• Atelectasis is the collapse of the lungs.
• This reflex also opens up collapsed portions of the lung.

CHEMICAL CONTROL:THE THREE MAIN ‘CHEMICALS’

OXYGEN

PO2 levels in blood.

CARBON DIOXIDE:

PCO2 levels in blood.

HYDROGEN ION:

Concentration in blood.

CO2 & [H+] act centrally while the Oxygen levels act on the peripheral chemoreceptors.

RESPIRATORY CHEMORECEPTORS

• CENTRAL:
• CHEMORECEPTOR ZONE:
• BILATERAL
• LOCATED IN THE MEDULLA
• JUST BENEATH IT’S VENTRAL SURFACE
• HIGHLY SENSITIVE TO PCO2 AND [H+]
• FUNCTIONS BY STIMULATING THE RESPIRATORY CENTERS:
• DRG,VRG & PTC.

CENTRAL CHEMORECEPTORS

• PRIMARY STIMULUS:
• [H+]
• PERHAPS THE ONLY IMPORTANT DIRECT STIMULUS FOR THE CENTRAL CHEMORECEPTOR CELLS (MEDULLARY CHEMORECEPTORS)
• But these ions do not cross the Blood Brain Barrier
• So, the blood PCO2 level has more effect as CO2 readily crosses the BBB.

STIMULATION BY CARBONDIOXIDE

• Is not direct.
• Even the indirect effect of CO2 is most potent. Why?
• Because CO2 easily crosses the BBB.
• Once it is across the BBB,
• CO2 + H2O -- H2CO3 -- H+ + HCO3-
• These increased H+ ions in the brain stimulate the medullary chemoreceptors.

QUANTITATIVE EFFECT OF H+ IONS

• The stimulatory effect of H+ ions increases in the first few hours.
• It then decreases in the next 1 to 2 days.
• It comes down to about 1/5th the initial effect.
• This is due to Renal readjustment of [H+] in the circulating blood.
• The kidneys increase blood HCO3.
• This bicarbonate binds with the free H+ ions in the blood & decreases their concentration.
• Bicarbonate also diffuses slowly past the BBB and decreases the H+ ions in the brain.
• Therefore the effect of H+ ions is:
• POTENT: Acutely
• WEAK : Chronically.

EFFECT OF CO2

• Change in PCO2 between 35 to 75mmHg causes peak increase in alveolar ventilation.
• 
  
• Change in the normal range causes less than tenth of change in alveolar ventilation.

EFFECT OF OXYGEN

• The partial pressure of Oxygen has no effect on the medullary chemoreceptors.
• 
  
• It only has an effect on the peripheral chemoreceptors.

PERIPHERAL CHEMORECEPTORS

• There are two pairs of chemoreceptors:
• Aortic Bodies: located at the arch of aorta.
• Carotid bodies: located at the branching of the common carotid arteries.
• Their functions are:
• To detect changes in the PO2
• To transmit nervous signals to the Respiratory Centers.
• These bodies have two types of special cells called glomus cells.
• The type 2 glomus cells have special ion channels sensitive to PO2.
• They fire the nerve endings and send signals via:
• Aortic bodies: Vagi.
• Carotid bodies: Hering nerve & Glossopharyngeal nerve.
• Both these bodies receive their own special blood supply through minute arteries, directly from the trunk.
• Their blood flow is roughly 20 times their own weight.
• THEY ARE ALL THE TIME EXPOSED ONLY TO ARTERIAL BLOOD.
• Decreased PO2 stimulates these chemoreceptors strongly.

ARTERIAL PO2 & IMPULSES IN AORTIC BODY

Decreased PO2 especially between 60 and 30mm Hg strongly stimulates the carotid bodies.

This is the range wherein the Hb saturation decreases

EFFECT OF PO2

• When PCO2 & [H+] are kept constantly normal,
• There is no effect if the PO2 is >100mmHg
• If it falls below 100mmHg, ventilation doubles upto 60 mmHg.
• It increases upto 5 times at very low PO2 levels

CO2 & H+

• They also stimulate the peripheral chemoreceptors.
• But their effects on the central or medullary chemoreceptors are more powerful.
• PCO2 stimulates the peripheral chemoreceptors 5 times as rapidly as it stimulates the central ones.
• So this is responsible for the rapid response to CO2 at the onset of exercise.

Lymph Vessels and Nodes of Lung

Lymphatic System (in brief ):

Major structures

lymph vessels

lymph nodes

lymph fluid

tonsils

Also:

spleen

thymus

Functions of the Lymph System

• lymph/o
• drain fluid from tissue spaces and return to it to the blood
• transport materials (nutrients, hormones and oxygen) to body cells
• carry away waste products to the blood
• transport lipids away from digestive system
• control of infection
• Lymph originates in blood plasma
• Interstitial fluid
• cleans and nourishes body tissues
• collects cellular debris, bacteria
• return to blood or lymph capillaries

Lymph Nodes

• located in lymph vessels
• small round or oval structures (filters)
• depositories for cellular debris
• bacteria and debris phagocytized
• inside are masses of tissue which contain WBCs (lymphocytes)
• almost always grouped 2 or 3 to 100
• invading cells destroyed in nodes and often swell as an indicator of the disease process

Spleen

sac-like mass of lymphatic tissue

filter for lymph

phagocytic cells

hemolytic

Thymus

lymphatic tissue

mediastinum

primary role: changes lymphocytes to T cells for cellular immunity

Menstrual Cycle

The Physiological Phenomenon for which the Human Race Exists as it does Today

Menstrual cycle

The physiological phenomenon in which the unused endometrium is shed and voided from the body as the menses or period or menstrual flow.

This term was derived in the context of human females who happen to cycle in about the same length of time as a lunar month, it is also applied to other species whose cycles are not one month long.

Human females are somewhat unusual

Females of most species are only receptive around the time of ovulation (release of a fertile egg)

A human female is more receptive around the time of ovulation

But that is not the only time she is receptive

Human females generally are receptive to sexual activity throughout their cycles

The average menstrual cycle in humans ranges about 20 to 40 days in length, with a statistical average of about 28 to 29 days.

By convention, the first day of a woman’s period is considered to be day 1 of her cycle.

The first 3 to 7 days are generally the menstrual flow phase and during this time, all hormones involved are at low levels.

Five hormones involved in controlling the female cycle

Gonadotropin releasing hormone (GnRH) secreted by the hypothalamus

Follicle-stimulating hormone (FSH) &

Lutenizing hormone (LH) secreted by the pituitary gland

Estrogen &

Progesterone secreted by ovaries

The first half of a woman’s cycle is the proliferative phase (follicular phase), during which the endometrium starts to thicken.

The pituitary secretes FSH which causes (usually one) follicle to mature and the ovaries to secrete estrogen.

The ovarian estrogen secretion gradually increases until just prior to ovulation.

This gradually supresses secretion of FSH and stimulates the hypothalamus to secrete a larger amount of GnRH which, in turn, triggers the pituitary to secrete a burst of LH, causing ovulation.

During the proliferative phase, a woman’s body temperature is low.

Sometimes there is a slight rise near the end of the phase during the pre-ovulatory burst of LH before it dips again at ovulation.

Throughout this phase, the cervical mucus becomes progressively clearer and thinner

Ovulation

Day 14 of an average 28-day cycle

In response to the surge of LH the rupture of the follicle and release of the egg

LH stimulates the remaining follicle cells to form a corpus luteum after ovulation

Sharp drop in the woman’s body temperature

cervical mucus becomes very thin and clear and forms “threads”

Heart muscles,as a pump and functions of valves

4 chambers:

Right and left atria

Right and left ventricles

4 valves:

Biscuspid valve between lft atrium and lft ventricles

Trcuspid valve between rt atrium and rt ventricles

2 semilunar valves ; one between lft ventricle and aorta and the other is between rt ventricle and pulmonary arteries

3 types of muscle:

Atrial muscle

Ventricular muscle

Specialized muscle:Excitatory muscle and conductory muscle

-Cardiac muscles are striated muscle with actin and myosin filaments sliding along side of each other as skeletal muscle.

-Syncytium:

The cardiac muscles are interconnected with each other by intercalated discs. At intercalated discs the membrane of cells fuses forming gap junctions through which adjacents cells can communicate with each other. These intercalated discs allows action potentail of one muscle cell to pass to other cells. By this way the whole heart muscle acts as a single unit. This property of heart muscle is called Syncytium.

2 types: Atrial and ventricular syncytium

-Atrium and ventricles are not directly connected. They are separated by fibrous tissues which insulates atria and ventricles.

-The impulses from atria are conducted to ventricles though specialezed conductive tissues called A-V bundle.

-Because of this insulation between atria and ventricles , atria contracts a short time ahead of ventricles.

Action potential in cardiac muscles

RMP: -85 mV

Peak/spike potential: +20 mV

After spkie potential it remains depolarised for about 0.2 sec called plateau phase and then only repolarization occurs. Plateau is the characteristics of heart muscle. Because of plateau ventricular muscles remains in contraction for 15 times longer duration than skeletal muscles.

Causes of plateau in Cardiac muscles

1.The cause of action potential in cardiac muscle is by opening of 2 types of channels:

a. fast Na ions channels

b. slow Na- Ca ions channels ( not present in skeletal muscles)

Slow Na-Ca ion channels opens slowly and remains opened for longer time, so large number of Na, Ca ions enters causing prolonged duration of depolarization and this causes plateau phase. The Ca ions that have influxed during plateau causes cardiac muscle contraction. But for skeletal muscle contraction Ca ions comes from sarcoplasmic reticulum .

2.After depolarization K ion permeability through cardiac mucle membrane decreases by 5 folds. So+ve ions remains inside the cell casuing plateau.

Velocity of conduction in cardiac muscles

Atrial , ventricular: 0.3 - 0.5 m/sec

Purkinje fiber: 4 m/sec

Refractory period: ventricles 0.25 – 0.30 sec (till plateau) ; atrium 0.15 sec

Relative refractory period: 0.05 sec, strong stimuli required for premature beats formation

Excitation – contraction coupling

-It is the mechanism by which action potential causes myofibrils to contract.

-It is same as skeletal muscle.in skeletal muscle only one source of Ca ions: from sarcoplasmic reticulum

-When action potential reaches T tubules it causes releae of Ca ions from t tubules itself and cisternae of sarcoplasmic reticulum.

-The difference is that there are two Ca ions source: one is from cisternae of sarcoplasmic reticulum and the another is from T tubules itself. Because of the extra Ca from T tubules the cardiac muscles contraction is strong. The diameter of T tubules is bigger and it also contains large number of negative ions which binds Ca ions and releases when action potential reaches T tubules.

Duration of contraction:

contraction begins just a few milliseconds after action potential starts and continues till few milliseconds after end of action potential.

Atrial: 0.2 sec

Ventricle: 0.3 sec

The Cardiac Cycle

The events that occurs from beginning of heart beat to the beginning of next is called cardiac cycle.

Action potential is generated in SA node , it is located in the superior lateral wall of right atrium near the opening of superior venacava. Then it travels through atria and then though A-V bundle into ventricles. At A-V node there is delay in conduction of 0.1 sec, because of this atria contracts prior to ventricles and so pumps blood in ventricles and then ventricles contracts and pumps blood out.

Diastole and systole:

Diastole is the phase of cardiac cycle during which heart remains relaxed and is filled with blood .

Systole is the phase during which heart remains contracted and pumps blood out.

Relationship of heart sounds to heart pumping

First heart sound:

is due to closure of A-V valves when ventricle starts to contract

Second heart sounds:

closure of aortic and pulmonary valves at end of systole

Relationship between left ventricular volume and intraventricular pressure during diastole and systole.

Preload and afterload

Preload is the pressure with which the ventricle starts to contract and is the end diastolic volume

Afterload is the pressure/load against which the ventricle has to contract and is the systolic pressure.

Regulation of heart pumping

1.Intrinsic regulation of heart pumping (Frank starling mechanism):

Within physiologic limit, the greater the heart muscle stretched during blood filling, greater is the force of contraction and greater quantity of blood is pushed into aorta. This is known as Frank-starling mechanism.

2.Control of heart by autonomic nervous system:

-sympathetic stimulation causes increase heart rate and increased force of contraction

-parasympathetic/vagus stimulation decreases heart rate

Effect of K & Ca on heart function

Inc. K ions in ECF:

-heart becomes dilated, flaccid

-HR decreases

-slows/blocks conduction of impulses through A-V node

-decreases the RMP

Inc Ca ions: opposite to Inc K ions

-spastic contraction

Dec Ca ions:

-flaccidity

Effect of temperature on heart function

Dec temperature:

decrease heart rate ; is due to less ions are permaeble to heart muscles membrane at low temp

Moderate inc temp:

contractile strength increased but high temp causes fatigue of muscle by inc metabolism.

Rhythmical Excitation of Heart

Excitatory & conductive system of heart

-sinoatrial /SA node, where impulse is generated

-internodal pathways conducts impulses to Atrio ventricular/A-V node

-A-V node delays impulse passing to ventricles

-A-V bundle conducts impulses from atria to ventricles

-lft and rt bundle branch of purkinje fiber carries impulses to all parts of ventricles.

SA node

-is a small, flat , ellipsoid strip of specialized cardiac muscle

-is located in superior posterolateral wall of rt atrium below and lateral to opening of SVC

-is directly connected to atrial muscle fiber, so AP generated in SA node immediately spreads to atria

-it is the pacemaker of heart

-RMP: -55 to -60 mV ( in ventricle is -85 to -90 mV), SA node is leaky to Na, Ca ions

-heart muscle have 3 types of pump: fast Na pump, slow Na-Ca pump, K pump

-in SA node fast Na pump is inactive and AP is due to slow Na- Ca pump & K pump

-SA node is self excitatory: this is due to high Na ions concentration in ECF and its membrane is leaky to Na ions . Because of this +ve Na ions enters itself and causes RMP to more than threshold leading to AP.

-Threshold: -40 mV

A-V node

-located in the posterior wall of rt atrium immediately behind tricuspid valve

-it delays the impulse conduction from atria to ventricles

-this delays allow atria to empty its content into ventricles before ventricles contract.

-it causes delay of 0.09 sec and another 0.04 sec is due to penetrating portion of AV bundle, also it takes 0.03 sec for impulse to come fromSA node to Av node. Total delay is 0.16 sec.

-slow conduction is due to dec gap junctions between conducting cells.

Ventricular purkinje system

-there is rapid transmission through ventricles due to specialized purkinje fibers.

-velocity is 1.5- 4 m/s and this is 6 time that in usual ventricle muscles

-high level of permeability at gap junctions

-impusle from SA node goes to ventricles only through purkinje fibers

-there is complete insulation between atria and ventricles except at AV bundle

-impulse travels in one direction only from Sa node to ventricles.

Control of excitation & conduction in heart

-SA node is the pacemaker of heart, discharging impulse at 70-80/min

-AV node, purkinje fiber can also exhibit intrinsic rhythmic excitation as SA node

-AV node can discharge impulse at rate of 40-60/min and purkinje at 15-40 /min if they are not stimulated from outside source.

- The dicharge rate of SA node is faster than the self excitatory discharge rate of others. Each time SA node discharges, its impulses is conducted through AV node and purkinje fibers and also depolarises their membrane. The depolarisation occurs before their membrane can reach to self excitatory threshold thus SA node inhibits impulse generation from AV node and purkinje fiber. Thus SA node is known as the pacemaker of heart.

Abnormal/Ectopic pacemakers

-Pacemaker elsewhere than SA node is known as ectopic pacemakers

-When SA node is not functioning at that time impulse is generated from AV node

-If there is AV block impulse will be generated from purkinje at rate of 15-40/min but atria will be beating normally. Purkinje will self generate impluse only after 5-20 sec because previously its function was suppressed by SA node. So during this time ventricles will not function and there will be lack of blood to brain and person faints and after sometime regains consciousnes. This is known as Stokes Adams Syndrome

Control of heart rhythm by autonomic nervous system

-Parasympathetic/vagus nerve mainly supplies SA node and AV node
-Sympathetic mainly supplies ventricles and also others.

-Vagus stimulation decreases heart rate and sometime even block heart and this is due to Ach release .Ach increases the permeability of K ions and makes membrane hyperpolarised(-65 to -75 mV)

-Sympathetic nerve increases heart rate by releasing norepinephrine which increases permeability to Na and Ca ions.

Electrocardiogram

When impulses passes through heart then electrical current also spreads to the surrounding tissues and to surface of body. When electrodes are placed on the surface then it can record the electrical activity . This is known as ECG.

ECG paper

ECG paper: contains small and large squares.

-Each small square is 1 mm and large square is 5mm

-Time is measured along horizontal line and each small square is 0.04 sec and each large square is 0.2 sec.

-Voltage is measured along vertical line and 10 mm is equal to 1 mV

-ECG paper moves at 25 mm/s speed, i.e. 1500 squares/min

ECG leads

3 types of leads:

Horizontal plane leads:

1.Chest leads/precordial leads: V1, V2, V3, V4,V5,V6

Frontal plane leads:

2.Bipolar leads/standard/Einthoven’s leads: I,II,III

3.Augmented unipolar leads: aVR, aVL, aVF

Placement of leads

Augmented leads:

aVR: right arm

aVL: left arm

aVF: left foot

Chest leads

V1: in 4th ICS at right sternal border

V2: in 4th ICS at lft sternal border

V3: midway between V2 and V4

V4: 5th ICS in lft MCL

V5: anterior axillary line in 5th ICS

V6: mid axillary line in 5th ICs

12 leaded ECG/EKG:

Chest leads:

Einthoven’s triangle:

Hexaxial reference system:

The function of the intrinsic conduction system is to initiate and distribute impulses so the heart depolarizes and contracts in an orderly manner from atria to ventricles. * As you must be able to identify the parts of the conduction system and trace the path of depolarization from the SA node to the purkinje fibers, we will review this.

* Since the SA node * has the highest rate of depolarization (75/min) , it starts the process by sending a wave of depolarization * through the myocardium of the atria. When this reaches the AV node * it depolarizes * and causes the Bundle of His * to depolarize.The depolarization travels into the septum through the bundle branches * * and from the bundle branches into the Purkinje fibers * * which cause depolarization of the ventricular myocardium. When the cardiac muscle cells of the myocardium, including the papillary muscles, the ventricles contract forcing blood out of the ventricles. *

Approximately 1% of the cardiac muscle cells are autorhythmic rather than contractile. * These specialized cardiac cells don’t contract but are specialized to initiate and conduct impulses through the heart to coordinate its activity. * These constitute the intrinsic cardiac conduction system. These autorhythmic cells constitute the following components of the intrinsic conduction system:

* the sinoatrial (SA) node, just inferior to the entrance of the superior vena cava into the right atrium,

* the atrioventricular node (AV) node, located just above the tricuspid valve in the lower part of the right atrium,

* the atrioventricular bundle (bundle of HIS), located in the lower part of the interatrial septum and which extends into the interventricular septum where it splits into right and left bundle branches * which continue toward the apex of the heart and the purkinje fibers * which branch off of the bundle branches to complete the pathway into the apex of the heart and turn upward to carry conduction impulses to the papillary muscles and the rest of the myocardium.

Although all of these are autorhythmic, they have different rates of depolarization. * For instance, the SA node * depolarizes at a rate of 75/min. * The AV node depolarizes at a rate of 40 to 60 beats per minute, * while the rest have an intrinsic rate of around 30 depolarizations/ minute. * Because the SA node has the fastest rate, it serves as the pacemaker for the heart. *

An ECG is a recording of the deflection waves caused by depolarization of the heart. * When the SA node * (the pacemaker) * depolarizes * the wave of depolarization that sweeps through the atria is recorded as the P wave * on the ECG. * The P wave indicates depolarization of the atria. * The QRS complex * is caused by depolarization of the ventricles. * Hidden in the QRS complex * is the repolarization of the atria since that occurs while the ventricles are depolarizing. * The T wave * represents repolarization of the ventricles. *

An enlarged QRS * * is indicative of hypertrophy (enlargement) of the ventricles. * * *

A prolonged QT interval * * is indicative of repolarization abnormalities * which increase susceptibility to various ventricular arrhythmias. *

Elevated T wave * is indicative of hyperkalemia, a condition which if not corrected may become life threatening. *

Likewise, a flat T wave * * is indicative of hypokalemia or ischemia. * *

Heart Blocks

Normal ECG

2nd Degree Block:

Not a QRS for each P wave

3rd Degree Block:

No P waves. Rate determined by autorhythmic cells in ventricles

The Frank Starling Law of the Heart states that

'' the more cardiac muscle is stretched within its physiological limits, the more forcibly it will contract. ''

This characteristic of cardiac muscle might be compared to a rubber band. The more you stretch the rubber band, the greater the force that is generated upon release. However if the rubber band is stretched too far, it may break. '' With respect to the heart’s ability to pump blood, increasing volumes of blood in the ventricles increasingly stretch the ventricular myocardium, generating greater force. '' The greater the force, the greater the volume of blood that is pumped out of the ventricle, up to the physiological limits of the myocardium.

ECG waves & genesis

P wave: normally upright , signifies atrial depolarisation

less than 2.5mm height and 0.11 sec duration

QRS complex: ventricular depolarisation N: 0.08 – 0.12 sec

T wave: ventricular repolarisation

U wave: it is positive deflection which comes after T wave. Is due to slow repolarization of interventricular purkinje fiber. Often it is not evident in ECG

R-R interval: distance between two successive R wave

P-R interval : time taken for impulse to travel from SA node to ventricles

0.12-0.22sec

QT interval: total time for ventricular depolarisation and repolarisation

less than 0.42 sec

Axis

Normal axis lies between -30 and +110 degree

Left axis deviation: -30 and -90 degree

Right axis deviation: +110 and +/- 180 degree

Intermediate axis : -90 and +/- 180 degree

Electrical axis of heart

Technique of reading and reporting ECG

1.Heart rate

2.Rhythm

3.Voltage

4.Axis

5.P wave

6.PR interval

7.QRS complex

8.ST segment

9.T wave

10.U wave

11.QT duration

12.Final diagnosis

Determination of axis

Many methods are there

Measure the overal height in leads I and aVF and then plot in graph paper. Then find the vector angle.

Heart rate

HR= 1500/ RR interval in small squares

Uses of ECG

Aids diagnosis, prognosis and treatment

Gives information regarding functioning of atria and ventricles

Identify damage to heart (infarction)

Identify abnormal rhythm and rate

Identify change in size of chambers of heart

Some Abnormalities in ECG

P wave:

a) p wave wide and notched (p-mitral)-left atrial hypertrophy

b) p wave tall and peaked ( p-pulmonale) –right atrial hypertrophy

QRS complex:

Tall QRS- ventricular hypertrophy

Tall peaked T wave- hyperkalemia

Low or inverted T wave- myocardial ischemia

U wave:

Prominent U wave- hypokalemia

ST segment:

Elevated with convexity upward-myocardial infaction

Depressed- angina pectoris

PR interval:

Increased PR interval -Bradycardia

Decreased PR interval- tachycardia

No PR interval- complete heart block

RVH

Coronary infarction

Sinus tachycardia

Ventricular tachycardia following extrasystole

Ventricular fibrillation

ECGs (lead II) showing

abnormal rhythms

A:Respiratory sinus arrhythmia.

B:Sinus arrest with vagal escape.

C:Atrial fibrillation.

D:Premature ventricular complex.

E:Complete atrioventricular block.

Wolf parkinson white ( WPW ) syndrome:

Extra path is formed between atrium and ventricle

Features:

Short PR interval

Wide QRS complex

Delta wave

Heart block:

1.First degree heart block: prolonged PR interval

2.Second degree heart block

a. Mobitz type I b. mobitz type II

3.Complete heart block