Exam 3 Flashcards
Circulatory system (blood)
Functions of Circulatory system
- Transportation
- Carries respiratory gases, metabolites.
- Nutrients - Regulation (hormonal, temperature)
- Protection
- Clotting, the circulatory system protects against blood loss from injury and foreign microbes or toxins introduced into the body.
- Immune, the immune function of the blood is performed by the leukocytes that protect against many disease.
Blood volume:
Males: 5-6 liters
Females: 4-5 liters
Vitamins, glucose, hormones, antibodies, proteins
in blood as well as oxygen etc
Blood is important for protection, respiration, nutrients
Blood:
Is a specialized connective tissue which
contains cellular and liquid components:
Blood cells – formed elements
Plasma – fluid portion
Hematocrit:
The percentage of the blood volume that consists of red blood cells
Males: 42–52%
Females: 37–47%
Hematocrit
male range is higher than female range
Plasma and blood cells
55% is plasma of blood
Blood plasma:
Straw-colored, sticky fluid portion of blood
Approximately 90% water.
Contains ions (Na+), nutrients, hormones, enzymes, antibodies, wastes, and proteins.
Three main plasma proteins:
-Albumin (60-80%) they are produced by the liver and provide the osmotic pressure needed to draw water from the surrounding tissue fluid into the capillaries.
-Globulins (alpha, beta, gamma. Alpha, beta are produced by the liver and function in transporting lipids and fat-soluble vitamins and function in immunity)
-Fibrinogen, is an important clotting factor produced by the liver.
The fluid from clotted blood, called serum.
Formed elements: Blood cells: Erythrocytes Leukocytes Platelets
Albumin is up to 80% of blood proteins
important for blood osmolarity
Albumin causes the BV to absorb fluid from cell and intrstitial space
prevents accumulation of fluid which leads to edema
Gamma globulins
can be used for treatment of Hepatitis
hepatitis is a viral infection of liver
no specific treatment for virus so we stimulate the immune cells to protect against the viral infection
Fibrinogen
clotting factor for blood clotting
Albumin is up to 80% of blood proteins
important for blood osmolarity
Albumin causes the BV to absorb fluid from cell and intrstitial space
prevents accumulation of fluid which leads to edema
Gamma globulins
can be used for treatment of Hepatitis
hepatitis is a viral infection of liver
no specific treatment for virus so we stimulate the immune cells to protect against the viral infection
Fibrinogen
clotting factor for blood clotting
Erythrocytes
Function: carries gasses, especially oxygen
It contains 280 million hemoglobin molecules (gives blood its red color), each hg molecule consists of four protein chain called globins, each of which is bound to one heme, a red-pigmented molecule that contains iron, the iron group of heme is able to combines with oxygen in the lungs and release oxygen in the tissues.
Production of RBCs:
Is mainly controlled by a hormonal mechanism. Cellular O2 deficiency is the initiating event in the production and release of the hormone erythropoietin (90% is produced in the glomeruli of the kidney, the rest mainly in the liver). Which stimulates red cell production in the bone marrow.
Life span of the RBC: 120 days.
Aged RBCs are removed from the blood in sinuses of the spleen and are degraded.
During intrauterine life when embryo has 4 weeks. The embryo is connected to the yolk sac
Wall of yolk sac functions
secretes germ cells XX for female and XY for male which migrate to gonads(testicle or ovary)
**stem cells for blood which gives nutrients to embryo during the first few months of pregnancy because the period there is no complete form of placenta
after first trimester then the yolk sac degenerates and placenta takes over to give nutrition to embryo
The first region of blood cells is from the wall of the yolk sac
After formation of the liver, then the liver secretes blood cells in fetus
after birth, bone marrow is the main part for the production of blood cells
(clinical point)
After 120 days the dead red blood cells are accumulated by the spleen and is converted into bilirubin
bilirubin is the product of dead red blood cells
During intrauterine life when embryo has 4 weeks. The embryo is connected to the yolk sac
Wall of yolk sac functions
secretes germ cells XX for female and XY for male which migrate to gonads(testicle or ovary)
**stem cells for blood which gives nutrients to embryo during the first few months of pregnancy because the period there is no complete form of placenta
after first trimester then the yolk sac degenerates and placenta takes over to give nutrition to embryo
The first region of blood cells is from the wall of the yolk sac
After formation of the liver, then the liver secretes blood cells in fetus
after birth, bone marrow is the main part for the production of blood cells
(clinical point)
After 120 days the dead red blood cells are accumulated by the spleen and is converted into bilirubin
bilirubin is the product of dead red blood cells
Leukocytes (White blood cells)
Neutrophils is for digestion and degradation of bacteria
it contains nuclei and mitochondria and can move in an amoeboid fashion. Because of this can squeeze through pores in capillary walls and move to a site of infection (Diapedesis or extravasation).
Two type of WBC:
- Agranular leukocytes (Lymphocytes, Monocyes)
- Granular leukocytes (eosinophils, basophils,
neutrophils) :
Basophils
active during inflammation
Lymphocyte
B cells release antibody
antibody detects antigen which then forms the antigen complex
T cell brings substance in
Monocyte
eating and digestion
Basophils
active during inflammation
Lymphocyte
B cells release antibody
antibody detects antigen which then forms the antigen complex
T cell brings substance in
Monocyte
eating and digestion
Lymphocytes:
Lymphocytes – compose 20–45% of WBCs
The most important cells of the immune system, their nucleus stains dark purple
Effective in fighting infectious organisms, Act against a specific foreign molecule (antigen)
Two main classes of lymphocyte
T cells – attack foreign cells directly
B cells – multiply to become plasma cells, secrete antibodies
Monocytes (e):
Monocytes: compose 4–8% of WBCs The largest leukocytes, Are phagocytic cells Nucleus: kidney shaped Transform into macrophages
Platelets (Thrombocytes)
Growth factor – involved in cell proliferation and cell growth
different types
Autocrine – some stem cells can control its own secretion
Role: blood clotting, by releasing serotonin, which stimulates constriction of the blood vessels, reducing the flow of blood to the injured area. Platelets also secrete growth factors , autocrine regulators.
Hematopoiesis
HP give rise to blood cells originate in the yolk sac of the human embryo and then migrate to the liver of the fetus. The stem cells then migrate to the bone marrow.
Erythropoiesis refers to the formation of erythrocytes, and leukopoiesis to the formation of leukocytes.
These processes occur in two classes of tissues after birth, myeloid and lymphoid.
Myeloid tissue is the red bone marrow of the long bones, sternum, pelvis, bodies of the vertebrae.
Lymphoid tissue includes the lymph nodes, tonsils, spleen, and thymus.
The bone marrow produces all of the different types of blood cells.
Formation of blood cells
Yolk sac -> liver -> bone marrow
Formation of blood cells
Yolk sac -> liver -> bone marrow
proerythroblast down
conversion of reticulocyte to erythrocyte requires 3 things
vitamin B 12
Fe2+
Folic acid
deficiency of one of the 3 items can lead to anemia
reduction of RBC
proerythroblast down
conversion of reticulocyte to erythrocyte requires 3 things
vitamin B 12
Fe2+
Folic acid
deficiency of one of the 3 items can lead to anemia
reduction of RBC
Cell lines in blood cell formation:
All blood cells originate in bone marrow
All originate from one cell type – blood stem cell
Lymphoid stem cells – give rise to lymphocytes
Myeloid stem cells – give rise to all other blood cells
Genesis of erythrocytes:
Committed cells are proerythroblasts
Remain in the reticulocyte stage for 1–2 days in circulation
Make up about 1–2% of all erythrocytes.
The production of red blood cells and synthesis of hemoglobin depends on the supply of iron, Vitamin B12, folic acid.
Disorders:
- Iron-deficiency anemia
- Pernicious anemia (inadequate amount of vitamin B12)
- Aplastic anemia , due to destruction of the bone marrow may be caused by chemical or by radiation.
Formation of leukocytes:
Granulocytes form from myeloblasts
Monoblasts enlarge and form monocytes
Platelet-forming cells from megakaryoblasts
Break apart into platelets
Deficiency of folic acid during pregnancy can affect the development of nervous system
can cause anecephalophy
brain can not develop = death of fetus
Deficiency of folic acid during pregnancy can affect the development of nervous system
can cause anecephalophy
brain can not develop = death of fetus
Disorders of erythrocytes
Polycythemia: abnormal excess of erythrocytes
Anemia: erythrocyte levels or hemoglobin concentrations are low
Normocytic anemia: such as blood loss
Microcytic anemia: in iron deficiency
Macrocytic anemia: in Vit B12 or Folate deficiency
Sickle cell disease: inherited condition, defective hemoglobin molecule
Erythrocytes distort into a sickle shape
Disorders of erythrocytes
Polycythemia: abnormal excess of erythrocytes
Polycythemia: abnormal excess of erythrocytes
Disorders of erythrocytes
Anemia: erythrocyte levels or hemoglobin concentrations are low
Anemia: erythrocyte levels or hemoglobin concentrations are low
Disorders of erythrocytes
Normocytic anemia: such as blood loss
Normocytic anemia: such as blood loss
Disorders of erythrocytes
Microcytic anemia: in iron deficiency
Microcytic anemia: in iron deficiency
Disorders of erythrocytes
Macrocytic anemia: in Vit B12 or Folate deficiency
Macrocytic anemia: in Vit B12 or Folate deficiency
Disorders of erythrocytes
Sickle cell disease: inherited condition, defective hemoglobin molecule
Erythrocytes distort into a sickle shape
Sickle cell disease: inherited condition, defective hemoglobin molecule
Erythrocytes distort into a sickle shape
Disorders of leukocytes:
Leukemia: a form of cancer
Classified as lymphoblastic or myeloblastic
Leukemia: a form of cancer
Classified as lymphoblastic or myeloblastic
Disorders of platelets:
Thrombocytopenia
Abnormally low concentration of platelets
Thrombocytopenia
Abnormally low concentration of platelets
Blood throughout life:
First blood cells develop with the earliest blood vessels
Mesenchyme cells cluster into blood islands
Late in the second month liver and spleen take over blood formation
Bone marrow becomes major hematopoietic organ at month 7
Polycythemia
AKA polyvera
over production of erythrocytes by bone marrow
could be primary or secondary
primary – main problem is in bone marrow
sign/symptoms – patient has increased RBC, WBC, Platelets
increased RBC can cause severe headache, vertigo(from hypertension)
spleen accumulates dead RBC = enlargement of spleen(splenomegaly) and liver(hepatomegaly)
increased hematocrit
weak immune system due to immature WBC
increased platelets leads to blood clotting which can lead to organs and block, myocardial infarction or stroke
Secondary – artificial due to over secretion of hormone Erythropoietin(on production of RBCs slide)
90% of hormone is secreted by kidney and 10% liver
Erythropoietin stimulates bone marrow for production of RBC
this is temporary
Polycythemia
AKA polyvera
over production of erythrocytes by bone marrow
could be primary or secondary
primary – main problem is in bone marrow
sign/symptoms – patient has increased RBC, WBC, Platelets
increased RBC can cause severe headache, vertigo(from hypertension)
spleen accumulates dead RBC = enlargement of spleen(splenomegaly) and liver(hepatomegaly)
increased hematocrit
weak immune system due to immature WBC
increased platelets leads to blood clotting which can lead to organs and block, myocardial infarction or stroke
Secondary – artificial due to over secretion of hormone Erythropoietin(on production of RBCs slide)
90% of hormone is secreted by kidney and 10% liver
Erythropoietin stimulates bone marrow for production of RBC
this is temporary
Normocytic anemia – losing blood volume during pregnancy
normal ish
Normocytic anemia – losing blood volume during pregnancy
normal ish
Microcytic anemia – due to deficiency of ion
Microcytic anemia – due to deficiency of ion
Macrocytic anemia – due to deficiency of B12 or folic acid
Macrocytic anemia – due to deficiency of B12 or folic acid
Sickle cell disease:
Sickle cell disease is an inherited blood disorder that affects red blood cells. People with sickle cell disease have red blood cells that contain mostly hemoglobin* S, an abnormal type of hemoglobin. Sometimes these red blood cells become sickle-shaped (crescent shaped) and have difficulty passing through small blood vessels.
Hemoglobin – is the main substance of the red blood cell. It helps red blood cells carry oxygen from the air in our lungs to all parts of the body. Normal red blood cells contain hemoglobin A.
Normal red blood cells are soft and round and can squeeze through tiny blood tubes (vessels). Normally, red blood cells live for about 120 days before new ones replace them.
Hemoglobin S and hemoglobin C are abnormal types of hemoglobin.
RBC has abnormal hemoglobin which carry 4 oxygen molecules
deficiency of hemoglobin leads to deficiency of oxygen supply
hypoxemia(deficiency of oxygen)
RBC has abnormal hemoglobin which carry 4 oxygen molecules
deficiency of hemoglobin leads to deficiency of oxygen supply
hypoxemia(deficiency of oxygen)
Sickle Cell
Clinical sign & symptoms:
Sickle cells are destroyed rapidly in the body of people with the disease causing anemia, jaundice and the formation of pigment gallstones. Almost all patients with sickle cell anemia have painful episodes (crises), which can last from hours to days. These crises can affect the bones of the back, the long bones, and the chest. Attacks of abdominal pain Bone pain Breathlessness Delayed growth and puberty Fatigue Fever Jaundice Paleness Rapid heart rate Ulcers on the lower leg
Treatment:
They should take supplements of folic acid.
Antibiotics and vaccines are given to prevent bacterial infections.
—–
Oxygen is last molecule for ATP electron acceptor
deficiency of oxygen supply leads to severe headache, weakness, irritates the sensory nerves(abdominal and joint pain), respiratory problems, weak immune system(fever), Jaundice
Jaundice is yellowish color of skin
due to high level of bilirubin(dead RBCs)
3 types of Jaundice
prehepatic
damaged RBCs
hemolytic
hepatic
cause is in liver
Alcoholics
failure of liver important protein production and iron which is important for RBC formation
posthepatic
closure or obstruction of common bile duct by stone
common bile duct carries bile from liver to intestine for emulsification of fat
obstruction and closure of duct means failure of release into small intestine
bile contains bilirubin
Treatment
folic acid, iron supplements
if bacterial infection then antibiotic too
Sickle cell class notes
Oxygen is last molecule for ATP electron acceptor
deficiency of oxygen supply leads to severe headache, weakness, irritates the sensory nerves(abdominal and joint pain), respiratory problems, weak immune system(fever), Jaundice
Jaundice is yellowish color of skin
due to high level of bilirubin(dead RBCs)
3 types of Jaundice
prehepatic
damaged RBCs
hemolytic
hepatic
cause is in liver
Alcoholics
failure of liver important protein production and iron which is important for RBC formation
posthepatic
closure or obstruction of common bile duct by stone
common bile duct carries bile from liver to intestine for emulsification of fat
obstruction and closure of duct means failure of release into small intestine
bile contains bilirubin
Treatment
folic acid, iron supplements
if bacterial infection then antibiotic too
Leukemia:
is cancer of the blood cells. It starts in the bone marrow, the soft tissue inside most bones. Bone marrow is where blood cells are made.
The bone marrow starts to make a lot of abnormal white blood cells, called leukemia cells. They don’t do the work of normal white blood cells, they grow faster than normal cells, and they don’t stop growing when they should.
Types of leukemia:
Acute
Chronic
Lymphocytic (or lymphoblastic) leukemia affects white blood cells called lymphocytes, it produces large numbers of mature white blood cells (lymphocytes).
Myelogenous leukemia affects white blood cells called myelocytes. It produces large numbers of immature and mature white blood cells (myelocytes).
Over production of immature WBC
immature WBC are not functional and can not protect the body
Lymphocytic – patient has large number of mature WBC, extremely high
Myeleocytic – mature and immature WBCs
Lukemia symptoms and treatment
Symptoms:
Fever and night sweats Headache Bleeding easily Bone or joint pain Swollen lymph nodes in the armpit, neck Getting a lot of infections weakness Losing weight
Treatment:
- Chemotherapy to kill leukemia cells using strong anti-cancer drugs;
- Interferon-alpha (INFa) therapy to slow the reproduction of leukemia cells and promote the immune system’s anti-leukemia activity;
- Radiation therapy to kill cancer cells by exposure to high-energy radiation.
- Stem cell transplantation (SCT) to enable treatment with high doses of chemotherapy and radiation therapy.
---- Patient has weak immune system risk for bacterial infection fever inflammation of lymphatic system weakness, losing weight
Treatment chemotherapy interferon-alpha – controls maturation of WBCs radiation stem cell transplantation
Blood vessels:
Composed of three layers (tunics)
Composed of three layers (tunics)
Tunica intima: composed of simple squamous epithelium
Tunica media: sheets of smooth muscle
Contraction: vasoconstriction Relaxation – vasodilation
Tunica externa: composed of connective tissue
Lumen: central blood-filled space of a vessel
Aorta(largest artery in body) -> artery -> arterioles -> capillary -> veniole -> large vein -> SVC/IVC
Aorta carries large amount of blood from left ventricle. By contraction of left ventricle we have ejection of large amount of blood into aorta. The pressure that exist in aorta comes from the LEFT VENTRICULAR CONTRACTION which is about 100mmHg. When the blood flow reaches the artery and arteriole the blood pressure decreases to 50mmHg. When it reaches the smaller diameter of the capillary and intersectional area with vein side the capillary shows resistance to blood flow. This is calls “Total Peripheral Resistance(TPR). The pressure drops to 20mmHg. In the veniole and large vein the pressure drops further to 4mmHg. The pressure in SVC and IVC is only 4mmHg.
Veins have smooth muscle in their walls which controls blood pressure which is controlled by ANS
BP is controlled by alpha 1 neurotransmitter by NE
BP = TPR * CO
Blood pressure
TPS – in capillary for total peripheral resistance
CO = cardiac output – the amount of blood ejected from the aorta per minute
approximately 5 liters per minute
Aorta(largest artery in body) -> artery -> arterioles -> capillary -> veniole -> large vein -> SVC/IVC
Aorta carries large amount of blood from left ventricle. By contraction of left ventricle we have ejection of large amount of blood into aorta. The pressure that exist in aorta comes from the LEFT VENTRICULAR CONTRACTION which is about 100mmHg. When the blood flow reaches the artery and arteriole the blood pressure decreases to 50mmHg. When it reaches the smaller diameter of the capillary and intersectional area with vein side the capillary shows resistance to blood flow. This is calls “Total Peripheral Resistance(TPR). The pressure drops to 20mmHg. In the veniole and large vein the pressure drops further to 4mmHg. The pressure in SVC and IVC is only 4mmHg.
Veins have smooth muscle in their walls which controls blood pressure which is controlled by ANS
BP is controlled by alpha 1 neurotransmitter by NE
BP = TPR * CO
Blood pressure
TPS – in capillary for total peripheral resistance
CO = cardiac output – the amount of blood ejected from the aorta per minute
approximately 5 liters per minute
Types of blood vessels:
Arteries: carry blood away from the heart
Veins: carry blood toward the heart
Capillaries: smallest blood vessels
The site of exchange of molecules
between blood and tissue fluid
Types of arteries:
1- Elastic arteries: the largest arteries, High elastin Diameters range from 2.5 cm to 1 cm (aorta and its major branches), also called conducting arteries,
2- Muscular (distributing) arteries
3- Arterioles: Smallest arteries
Veins:
Conduct blood from capillaries toward the heart
Blood pressure is much lower than in arteries
Smallest veins – called venules, diameters from 8–100 µm
Smallest venules – called postcapillary venules, Venules join to form veins
Tunica externa is the thickest tunic in veins
Some veins particularly in the limbs have valves
Skeletal muscle pump: muscle press the veins and push the blood toward heart
vascular anastomoses Vasa vasorum
Capillaries:
Smallest blood vessels, Diameter from 8–10 µm, RBCs pass through single file Capillary bed: Network of capillaries running through tissues
Low permeability capillaries:
Blood-brain barrier
Highly selective, only vital substances pass through.
Not a barrier against O2, CO2 and some anesthetics.
Sinusoids:
Wide, leaky capillaries found in
spleen, liver…
When TPR or CO increases then BP increases = hypertension
BP = TPR * CO
When TPR or CO increases then BP increases = hypertension
BP = TPR * CO
Pericardium is a thin membrane which covered heart
Pericardium is a thin membrane which covered heart
Structure of the heart
Your heart is located between your lungs in the middle of your chest.
Pericardium
Myocardium
Papillary muscle, Chordae tendineae
The heart has 4 chambers:
left and right atria,
left and right ventricles.
A wall of muscle called the septum separates the left and right atria and the left and right ventricles.
The left ventricle is the largest and strongest chamber in your heart. The left ventricle’s chamber walls are only about a half-inch thick, but they have enough force to push blood through the aortic valve and into your body.
Pericardium protects heart from external trauma
Myocardium
heart muscle
Endocardium
internal layer of heart walls
Chordae tendineae connects valve and papillary muscle
3 papillary on right and 2 on left
Pericardium protects heart from external trauma
Myocardium
heart muscle
Endocardium
internal layer of heart walls
Chordae tendineae connects valve and papillary muscle
3 papillary on right and 2 on left
The Heart Valves
Four types
Four types of valves regulate blood flow through your heart:
- The tricuspid valve regulates blood flow between the right atrium and right ventricle.
- The pulmonary valve controls blood flow from the right ventricle into the pulmonary arteries, which carry blood to your lungs to pick up oxygen.
- The mitral valve lets oxygen-rich blood from your lungs pass from the left atrium into the left ventricle.
- The aortic valve opens the way for oxygen-rich blood to pass from the left ventricle into the aorta, your body’s largest artery, where it is delivered to the rest of your body.
The Heart Valves
Tricuspid valve
The tricuspid valve regulates blood flow between the right atrium and right ventricle.
The Heart Valves
pulmonary valve
The pulmonary valve controls blood flow from the right ventricle into the pulmonary arteries, which carry blood to your lungs to pick up oxygen.
The Heart Valves
mitral valve
The mitral valve lets oxygen-rich blood from your lungs pass from the left atrium into the left ventricle.
The Heart Valves
aortic valve
The aortic valve opens the way for oxygen-rich blood to pass from the left ventricle into the aorta, your body’s largest artery, where it is delivered to the rest of your body.
Circulation Through the Heart
After flowing through the body, blood enters the heart at the right atrium. From the right atrium, it passes through the right atrioventricular valve and into the right ventricle. When the right ventricle contracts, it ejects the blood out of the heart through the pulmonary valve and into the pulmonary artery to the lungs.
After passing through the lungs, removing CO2 and picking up oxygen (O2), the blood returns through the pulmonary vein to the left atrium. From here the blood enters the left ventricle through the left atrioventricular valve.
When the left ventricle contracts, blood is ejected through the aortic valve into the aorta and out to the body.
Superior and inferior vena cava collect deoxygenated blood from upper and lower parts of the body and release the content into the right atrium. RA contracts and releases its contents into right ventricle through tricuspid valve. The RV contracts and ejects large amount of blood into pulmonary artery. Pulmonary artery then becomes left and right pulmonary arteries which carry deoxygenated blood to lung tissue for gas exchange. After gas exchange in lungs then the lung tissue releases oxygen molecules into pulmonary capillary . The pulmonary capillary becomes the pulmonary veins. Pulmonary veins carry fresh oxygenated blood to left atrium. LA contracts and releases fresh oxygenated blood into left ventricle through the mitral(bicuspid) valve. The LV contracts and ejects large amount of blood into aorta. The aorta carries fresh blood to head and neck, upper limb, and lower part of body.
Aorta has 3 parts ascending arch descending enters into abdominal cavity and becomes abdominal aorta which branches to supply organs
Superior and inferior vena cava collect deoxygenated blood from upper and lower parts of the body and release the content into the right atrium. RA contracts and releases its contents into right ventricle through tricuspid valve. The RV contracts and ejects large amount of blood into pulmonary artery. Pulmonary artery then becomes left and right pulmonary arteries which carry deoxygenated blood to lung tissue for gas exchange. After gas exchange in lungs then the lung tissue releases oxygen molecules into pulmonary capillary . The pulmonary capillary becomes the pulmonary veins. Pulmonary veins carry fresh oxygenated blood to left atrium. LA contracts and releases fresh oxygenated blood into left ventricle through the mitral(bicuspid) valve. The LV contracts and ejects large amount of blood into aorta. The aorta carries fresh blood to head and neck, upper limb, and lower part of body.
Aorta has 3 parts ascending arch descending enters into abdominal cavity and becomes abdominal aorta which branches to supply organs
Systemic circulations
Systemic circulation is the portion of the cardiovascular system which carries oxygenated blood away from the heart, to the body, and returns deoxygenated blood back to the heart. The term is contrasted with pulmonary circulation.
Oxygenated blood from the lungs leaves the left heart through the aorta, from where it is distributed to the body’s organs and tissues, which absorb the oxygen, through a complex network of arteries, arterioles, and capillaries. The deoxygenated blood is then collected by venules, from where it flows first into veins, and then into the inferior and superior venae cavae, which return it to the right heart, completing the systemic cycle. The blood is then re-oxygenated through the pulmonary circulation before returning again to the systemic circulation.
Systemic circulation
connection between body and heart by SVC and IVC which carry deoxygenated blood from body to heart
Aorta takes back fresh blood from heart to entire body
Systemic circulation
connection between body and heart by SVC and IVC which carry deoxygenated blood from body to heart
Aorta takes back fresh blood from heart to entire body
Systemic circulation
connection between body and heart by SVC and IVC which carry deoxygenated blood from body to heart
Aorta takes back fresh blood from heart to entire body
Pulmonary circulation
Pulmonary circulation is the portion of the cardiovascular system which carries oxygen-depleted blood away from the heart, to the lungs, and returns oxygenated blood back to the heart. The term is contrasted with systemic circulation.
Oxygen-depleted blood from the body leaves the right heart through the pulmonary arteries, which carry it to the lungs, where red blood cells release carbon dioxide and pick up oxygen during respiration.
The oxygenated blood then leaves the lungs through the pulmonary veins, which return it to the left heart, completing the pulmonary cycle.
The blood is then distributed to the body through the systemic circulation before returning again to the pulmonary circulation.
Connection between heart and lungs
2 pulmonary arties carry deoxygenated blood from heart to lungs
4 pulmonary veins carry fresh oxygenated blood from lungs to heart
Connection between heart and lungs
2 pulmonary arties carry deoxygenated blood from heart to lungs
4 pulmonary veins carry fresh oxygenated blood from lungs to heart
Connection between heart and lungs
2 pulmonary arties carry deoxygenated blood from heart to lungs
4 pulmonary veins carry fresh oxygenated blood from lungs to heart
Aorta, artery, arteriole contain smooth muscle
Innervation is by Alpha 1(vasoconstriction) and Beta 2(relaxation) adrenergic receptors
by ANS
The pressure that exist in the arteriole system is much higher than in the venous system
the pressure comes from ventricular contraction of heart
the volume of blood which circulates in arteriole is “stressed volume”(under high pressure)
Capillary lacks smooth muscle
contains pores for gas exchange, nutrients, fluid to pass through
Aorta, artery, arteriole contain smooth muscle
Innervation is by Alpha 1(vasoconstriction) and Beta 2(relaxation) adrenergic receptors
by ANS
The pressure that exist in the arteriole system is much higher than in the venous system
the pressure comes from ventricular contraction of heart
the volume of blood which circulates in arteriole is “stressed volume”(under high pressure)
Capillary lacks smooth muscle
contains pores for gas exchange, nutrients, fluid to pass through
Hemodynamics
Components of the vasculature
Arteries
Arteries
- deliver oxygenated blood to the tissues.
- are thick-walled, with extensive elastic tissue and smooth muscle.
- are under high pressure.
- The blood volume contained in the arteries is called the stressed volume.
Hemodynamics
Components of the vasculature
Arterioles
Arterioles
- are the smallest branches of the arteries.
- are the site of highest resistance in the cardiovascular system.
- have a smooth muscle wall that is extensively innervated by autonomic nerve fibers.
- Arteriolar resistance is regulated by the autonomic nervous system (ANS).
- Alpha1-Adrenergic receptors are found on the arterioles of the skin, splanchnic, and renal circulations.
- Beta2-Adrenergic receptors are found on arterioles of skeletal muscle.
Hemodynamics
Components of the vasculature
Capillaries
Capillaries
- consist of a single layer of endothelial cells surrounded by basal lamina.
- are thin-walled.
- are the site of exchange of nutrients, water and gases.
Hemodynamics
Components of the vasculature
Venules
Venules
-are formed from merged capillaries.
Hemodynamics
Components of the vasculature
Veins
Veins
–progressively merge to form larger veins. The largest vein, the vena cava, returns blood to the heart.
-are thin-walled.
-are under low pressure.
-contain the highest proportion of the blood in the cardiovascular system.
-The blood volume contained in the veins is called the unstressed volume.
-have alpha 1-adrenergic receptors.
Velocity of blood flow
-can be expressed by the following equation:
V= Q/A
V=velocity (cm/sec)
Q=blood flow (ml/min)
A= cross-sectional area (cm2)
Velocity is directly proportional to blood flow and inversely proportional to the cross-sectional area at any level of the cardiovascular system.
For example, blood flow velocity is higher in the aorta than in the sum of all of the capillaries . The lower velocity of blood flow in the capillaries optimizes conditions for exchange of substances across the capillary wall.
Velocity depends on cross-sectional area
capillary has higher cross sectional area so blood flows slower in capillaries
Velocity depends on cross-sectional area
capillary has higher cross sectional area so blood flows slower in capillaries
Velocity depends on cross-sectional area
capillary has higher cross sectional area so blood flows slower in capillaries
Blood flow
-can be expressed by the following equation:
Q=P/R
Or
Cardiac output= Mean arterial pressure- Right atrial pressure
Total peripheral resistance (TPR)
Q=flow or cardiac output (ml/min)
P= pressure gradient (mm Hg)
R =resistance or total peripheral resistance (mm Hg/ml/min)
- The equation for blood flow (or cardiac output) is analogous to Ohm’s law for electrical circuits (I= V/R), where flow is analogous to current, and pressure is analogous to voltage.
- The pressure gradient (P) drives blood flow.
- Thus, blood flows from high pressure to low pressure.
- Blood flow is inversely proportional to the resistance of the blood vessels.
Blood flow depends on QPR and cardiac output
Blood flow depends on QPR and cardiac output
Blood flow depends on QPR and cardiac output
Resistance
-Poiseuille’s equation gives factors that change the resistance of blood vessels.
R= (8 n l)/
(r)(4)
R= resistance
n= viscosity of blood
l=length of blood vessel
r4= radius of blood vessel to the fourth power
- Resistance is directly proportional to the viscosity of the blood. For example, increasing viscosity by increasing hematocrit will increase resistance and decrease blood flow.
- Resistance is directly proportional to the length of the vessel.
Resistance depends on
diameter of blood vessel(radius)
concentration of blood stream(viscosity)
length of blood vessel
Resistance depends on
diameter of blood vessel(radius)
concentration of blood stream(viscosity)
length of blood vessel
Resistance depends on
diameter of blood vessel(radius)
concentration of blood stream(viscosity)
length of blood vessel
Capacitance (compliance)
- describes the distensibility of blood vessels.
- is inversely related to elastance. The greater the amount of elastic tissue in a blood vessel, the higher the elastance, and the lower the compliance.
- is expressed by the following equation:
C=V/P
C= capacitance or compliance (ml/mm Hg)
V= volume (ml)
P=pressure (mm Hg)
- is directly proportional to volume and inversely proportional to pressure.
- describes how volume changes in response to a change in pressure.
- is much greater for veins than for arteries. As a result, more blood volume is contained in the veins (unstressed volume) than in the arteries (stressed volume).
- Changes in the capacitance of the veins produce changes in unstressed volume. For example, a decrease in venous capacitance decreases unstressed volume increases stressed volume by shifting blood from the veins to the arteries.
- Capacitance of the arteries decreases with age, as a person ages, the arteries become stiffer and less distensible.
More elastic fiber means the wall is thicker(stronger)
Less elastic fiber means thinner(weaker)
When thick wall in blood vessel then the thickness covers more internal environment and is thicker than venous system
The blood flow that exist in artery is a little bit lower than venous system
BUT arteriole pressure is much higher than venous system
The pressure in venous system is only 4mm Hg
Capacity depends on amount of elastic fiber
thicker fiber = lower capacity but increased pressure
More elastic fiber means the wall is thicker(stronger)
Less elastic fiber means thinner(weaker)
When thick wall in blood vessel then the thickness covers more internal environment and is thicker than venous system
The blood flow that exist in artery is a little bit lower than venous system
BUT arteriole pressure is much higher than venous system
The pressure in venous system is only 4mm Hg
Capacity depends on amount of elastic fiber
thicker fiber = lower capacity but increased pressure
Pressure profile in blood vessels
- As blood flows through the systemic circulation, pressure decreases progressively because of the resistance to blood flow.
- Thus, pressure is highest in the aorta and large arteries and lowest in the vena cavae.
- The largest decrease in pressure occurs across the arterioles because they are the site of highest resistance.
Mean pressure in the systemic circulation are as follows:
Aorta, 100 mm Hg
Arterioles, 50 mm Hg
Capillaries, 20 mm Hg
Vena cava, 4 mm Hg
Arterial pressure
Blood pressure (BP) is a force exerted by circulating blood on the walls of blood vessels. -is not constant during a cardiac cycle. It is pulsatile.
- Systolic pressure
- is the highest arterial pressure during a cardiac cycle.
- is measured after the heart contracts (systole) and blood is ejected into the arterial system. - Diastolic pressure
- is the lowest arterial pressure during a cardiac cycle.
- is measured when the heart relaxed (diastole) and blood is returning to the heart via the veins. - Pulse pressure
-is the different between the systolic and diastolic pressures.
-The most important determinant of pulse pressure is stroke volume.
As blood is ejected from the left ventricle into the arterial system, systolic pressure increases because of the relatively low capacitance of the arteries. Because diastolic pressure remains unchanged during ventricular systole, the pulse pressure increases to the same extent as the systolic pressure.
-Decreases in capacitance, such those that occur with the aging process, cause increases in pulse pressure. - Mean arterial pressure
- can be calculated approximately as diastolic pressure plus one-third of pulse pressure.
Systolic pressure
pressure that exist in ventricle during contraction
Diastolic pressure
pressure that exist in in ventricle during relaxation
Pulse pressure
difference between systolic and diastolic
Clinical point arteriole pressure(any artery) is higher than venous pressure venous pressure is higher than atrial pressure(atrium in heart)
Systolic pressure
pressure that exist in ventricle during contraction
Diastolic pressure
pressure that exist in in ventricle during relaxation
Pulse pressure
difference between systolic and diastolic
Clinical point arteriole pressure(any artery) is higher than venous pressure venous pressure is higher than atrial pressure(atrium in heart)
Venous pressure
- is very low.
- The veins have a high capacitance and therefore, can hold large volumes of blood at low pressure.
2 factors
valve in vein
skeletal muscle covers veins
contraction of skeletal muscle then it increases pressure which is helpful for blood flow in venous system
Atrial pressure
Atrial pressure
- is even lower than venous pressure.
- Left atrial pressure is estimated by the pulmonary wedge pressure. A catheter, inserted into the smallest branches of the pulmonary artery, makes almost direct contact with the pulmonary capillaries. The measured pulmonary capillary pressure is approximately equal to the left atrial pressure.
Hypertension
Primary or essential hypertension
This is on test
Environmental factors (dietary Na+, obesity, and stress), whatever the responsible pathogenic mechanisms, they must lead either to increased total peripheral vascular resistance (TPR) by inducing vasoconstriction or to increased cardiac output (CO), or both. Because BP =CO x TPR (resistance).
Sympathetic nervous system and renin-angiotensin-aldosteron system have received the most attention for the pathophysiology of hypertension, both can increase CO and TPR.
Na+: Abnormal Na+ transport across the cell wall due to a defect in or inhibition of the Na+/K+ pump or because of increased permeability to the Na+. Increased intracellular Na+, which makes the cell more sensitive to sympathetic stimulation. Since Ca2+ follows Na+, accumulation of intracellular Ca2+ is responsible for the increased sensitivity.
Deficiency of a vasodilator substance: prostaglandin, bradykinin.
Know this slide. Its on test
What is blood pressure?
the pressure that exist in blood vessels from blood flow on wall of blood vessel
BP = CO * TPR
TPR – resistance in capillaries
CO – cardiac output the amount of blood per minute is about 5 liters
Hyper tension types
Primary
Secondary
We do not know the exact cause of primary hypertension
secondary we know and can treat
Obesity which is associated with endocrine disorder(like type 2 diabetes)
stress increases cortisol hormone(stress hormone)
increases appetite which causes obesity
increases TPR and systolic and diastolic pressures
Clinical point
Tumor in sympathetic system
over stimulation/secretion of NE leads to alpha 1 oversecretion = vasoconstriction
***any factor(s) which leads to contraction or vasoconstriction, obstruction, or destruction of BV leads to hypertension
After depolarization then calcium enter cells
Ca2+ is extremely important for contraction of any muscle
Hypercalcemia leads to hyper tension
hypocalcemia can impact heart function and blood pressure
Prostaglandid and bradykinin are vasodilators
deficiency of these causes hypertension
Know this slide. Its on test
What is blood pressure?
the pressure that exist in blood vessels from blood flow on wall of blood vessel
BP = CO * TPR
TPR – resistance in capillaries
CO – cardiac output the amount of blood per minute is about 5 liters
Hyper tension types
Primary
Secondary
We do not know the exact cause of primary hypertension
secondary we know and can treat
Obesity which is associated with endocrine disorder(like type 2 diabetes)
stress increases cortisol hormone(stress hormone)
increases appetite which causes obesity
increases TPR and systolic and diastolic pressures
Clinical point
Tumor in sympathetic system
over stimulation/secretion of NE leads to alpha 1 oversecretion = vasoconstriction
***any factor(s) which leads to contraction or vasoconstriction, obstruction, or destruction of BV leads to hypertension
After depolarization then calcium enter cells
Ca2+ is extremely important for contraction of any muscle
Hypercalcemia leads to hyper tension
hypocalcemia can impact heart function and blood pressure
Prostaglandid and bradykinin are vasodilators
deficiency of these causes hypertension
Hypertension(know this on test)
Secondary hypertension
Secondary hypertension can be caused by conditions that affect your kidneys, arteries, heart or endocrine system. Secondary hypertension can also occur during pregnancy.
- Disorders of the adrenal gland
- Cushing’s syndrome (a condition caused by an overproduction of cortisol)
- Hyperaldosteronism (too much aldosterone)
- Pheochromocytoma (a rare tumor that causes over secretion of hormones like adrenaline and NA).
- Kidney disease: polycystic kidney disease, kidney tumor, kidney failure, or a narrow or blocked main artery supplying the kidney.
- Drugs: such as corticosteroids (anti-inflammatory drugs like prednisone), leads to increased systolic, diastolic pressures and increases arterial resistance.7. Nonsteroidal anti-inflammatory drugs (Motrin, Aleve,), weight loss drugs (such as Meridia). Salt and water retention, sympathetic activity, loss of renal vasodilation.
- Coarctation of the aorta, a birth defect in which the aorta is narrowed
- Preeclampsia, a condition related to pregnancy, endothelial dysfunction in the maternal blood vessels.
- Thyroid and parathyroid problems
Know this slide – on test
Adrenal gland
adrenal cortex surrounds adrenal medulla
adrenal cortex secretes 3 hormones
aldosterone
when BP is low then enzyme Renin is secreted from kidney
Renin converts Angiotensinogen(from liver protein) into Ag1(inactive form)
ACE(from lung tissue) converts AG1 -> Ag2
Ag2 acts as
vasoconstrictor
aldosterone release from adrenal cortex in to blood stream
blood stream carries Aldosterone to nephron in kidney
Aldosterone binds to its receptor on nephron collecting tubule
Capillary then absorbs Na+, Cl-, H2O, and HCO3- into blood
H+ and K+ release into urine
***this means fluid absorption which increases blood pressure
cortisol
increases TPR, systolic, and diastolic pressures
androgen
adrenal medulla
adrenaline(aka epinepherine)
noradrenaline(aka NE)
binds to alpha 1 adrenergic receptor leading to vasoconstriction
all but androgen if oversecreted lead to hypertension
Know this slide – on test
Adrenal gland
adrenal cortex surrounds adrenal medulla
adrenal cortex secretes 3 hormones
aldosterone
when BP is low then enzyme Renin is secreted from kidney
Renin converts Angiotensinogen(from liver protein) into Ag1(inactive form)
ACE(from lung tissue) converts AG1 -> Ag2
Ag2 acts as
vasoconstrictor
aldosterone release from adrenal cortex in to blood stream
blood stream carries Aldosterone to nephron in kidney
Aldosterone binds to its receptor on nephron collecting tubule
Capillary then absorbs Na+, Cl-, H2O, and HCO3- into blood
H+ and K+ release into urine
***this means fluid absorption which increases blood pressure
cortisol
increases TPR, systolic, and diastolic pressures
androgen
adrenal medulla
adrenaline(aka epinepherine)
noradrenaline(aka NE)
binds to alpha 1 adrenergic receptor leading to vasoconstriction
all but androgen if oversecreted lead to hypertension
Hypertension Symptoms
Usually asymptomatic Headache Fatigue Shortness of breath Dizziness Convulsion Changes in vision (Blurred vision, Double vision) Nausea Vomiting Anxiety Increased sweating Nose bleeds Tinnitus - ringing or buzzing in ears Heart palpitations General feeling of unwellness Increased urination frequency Flushed face Pale skin
Severe headache, vomiting, anxiety, sweating, sleep disorder, vertigo, palpitation, nose bleeding, weakness
Drugs to treat High Blood Pressure
Angiotensin-converting enzyme (ACE) inhibitors, Captopril, Ramipril
Angiotensin || receptor blockers (ARBs) , Valsartan
Diuretics, Thiazide diuretics such as hydrochlorothiazide
Calcium channel blockers, Felodipine, Benidipine
Beta-adrenergic blocking agents, Propranolol
ACE inhibitors can block ACE
Ag2 receptor blockers
Aldosterone receptor blockers
spironolactone
P wave
The P wave represents the wave of depolarization that spreads from the SA node throughout the atria, and is usually 0.08 to 0.1 seconds (80-100 ms)
in duration.
-represents atrial depolarization.
-does not include atrial repolarization,
which is buried in the QRS complex.
---- P wave first half is depolarization and contraction of right atrium second half is left atrium relaxation phase can not be seen on EKG might be part of Q
PR interval
The period of time from the onset of the P wave to the beginning of the QRS complex is termed the P-R interval, which normally ranges from 0.12 to 0.20 seconds in duration. This interval represents the time between the onset of atrial depolarization and the onset of ventricular depolarization.
*** If the P-R interval is >0.2 sec, there is an AV conduction block.
---- PR interval between P wave and QRS complex depolarization and stimulation of AV node 0.1 -0.2 seconds
QRS complex
The duration of the QRS complex is normally 0.06 to 0.1 seconds. This relatively short duration indicates that ventricular depolarization normally occurs very rapidly.
*** If the QRS complex is prolonged (> 0.1 sec), conduction is impaired within the ventricles. This can occur with bundle branch blocks or whenever a ventricular foci (abnormal pacemaker site) becomes the pacemaker driving the ventricle.
***Ectopic foci are abnormal pacemaker sites within the heart (outside of the SA node) that display automaticity. Such an ectopic foci nearly always results in impulses being conducted over slower pathways within the heart, thereby increasing the time for depolarization and the duration of the QRS complex.
QRS complex
duration 0.06-0.1 second
shows depolarization and contraction of both ventricles
Ectopic foci
abnormal contraction of ventricle
example
post myocardial infarction
the healed tissue may have spontaneous depolarization which can send signals to different parts of heart
may shows multiple QRS back to back on EKG
ST segment
-is the segment from the end of the S wave
to the beginning of the T wave.
-represents the period when the ventricles completely
are depolarized.
*** The ST segment is important
in the diagnosis of ventricular ischemia or hypoxia
because under those conditions,
the ST segment can become
either depressed or elevated.
—-
ST segment
between WRS complex and T wave
T wave is relaxation phase of ventriculars
between depolarization and repolarization of ventricles
Clinical point
elevated or depressed ST segment shows positive sign for myocardial infarction
T wave
The T wave represents ventricular repolarization and is longer in duration than depolarization (i.e., conduction of the repolarization wave is slower than the wave of depolarization).
Sometimes a small positive U wave may be seen following the T wave.
This wave represents the last remnants of ventricular repolarization. Inverted or prominent U waves indicates underlying pathology or conditions affecting repolarization.
T Wave
repolarization and relaxation of ventricles
QT interval
-is the interval from the beginning of the Q wave to the end of the T wave.
The Q-T interval represents the time for both ventricular depolarization and repolarization to occur, and therefore roughly estimates the duration of an average ventricular action potential. This interval can range from 0.2 to 0.4 seconds depending upon heart rate.
- ** At high heart rates, ventricular action potentials shorten in duration, which decreases the Q-T interval. Because prolonged Q-T intervals can be diagnostic for susceptibility to certain types of tachyarrhythmias.
- represents the entire period of depolarization and repolarization of the ventricles.
QT interval
0.2-0.4 seconds
shows contraction and relaxation of both ventricles
Tachyarrhythmias
abnormal
especially the contraction
Cardiac action potentials
Ventricles, atria and the Purkinje system
Phase 0
-have stable resting membrane potentials of about
-90mV.
This value approaches the K+ equilibrium potential.
-Action potential are of long duration, especially in Purkinje fibers, where they last 300 msec.
-is the upstroke of the action potential.
-is caused by a transient increase in Na+ conductance. This increase results in an inward Na+ current that depolarizes the membrane.
At the peak of the action potential, the membrane potential approaches the Na+ equilibrium potential.
Phase 0
opening of sodium channels which enters cells
leads to depolarization of atrial ventricular Purkinje fiber cells
Phase 1
potassium ions leave cells
Cardiac action potentials
Ventricles, atria and the Purkinje system
Phase 1
- is a brief period of initial repolarization.
- Initial repolarization is caused by an outward current, in part because of the movement of K+ ions (favored by both chemical and electrical gradients) out of the cell and in part because of a decrease in Na+ conductance.
Cardiac action potentials
Ventricles, atria and the Purkinje system
Phase 2
–is the plateau of the action potential
- is caused by a transient increase in Ca2+ conductance, which results in an inward Ca2+ current, and by an increase in K+ conductance.
- During phase 2, outward and inward currents are approximately equal, so the membrane potential is stable at the plateau level.
Cardiac action potentials
Ventricles, atria and the Purkinje system
Phase 3
- is repolarization.
- During phase 3, Ca2+ conductance decreases, and K+ conductance increases and therefore predominates.
- The high K+ conductance results in a large outward K+ current (Ik) which hyperpolarizes the membrane back toward the K+ equilibrium potential.
Cardiac action potentials
Ventricles, atria and the Purkinje system
Phase 4
- is the resting membrane potential.
- is a period during which inward and outward current (Ik1) are equal and the membrane potential approaches the K= equilibrium potential.
Cardiac action potentials
Sinoatrial node
Phase 0
- is normally the pacemaker of the heart.
- has an unstable resting potential.
-is upstroke of the action potential.
-is caused by an increase in Ca2+ conductance.
This increase causes an inward Ca2+
current that drives the membrane potential
toward the Ca+ equilibrium potential.
-The ionic basis for phase 0 in SA node
is different from that in the ventricles, atria and Purkinje fibers (where it is result of an inward Na+ current.)
Cardiac action potentials
Sinoatrial node
Phases 1 and 2
Phases 1 and 2
-are not present in the SA node action potential.
Cardiac action potentials
Sinoatrial node
Phase 3
- is repolarization.
- is caused by an increase in K+ conductance. This increase results in an outward K+ current that causes repolarization of the membrane potential.
Cardiac action potentials
Sinoatrial node
Phase 4
- is slow depolarization.
- accounts for the pacemaker activity of the SA node (automaticity).
- is caused by an increase in Na+ conductance, which results in an inward Na+ current called If (slow depolarization, produced by the opening of Na+ channels and an inward Na+ current called If). (“f” which stands for funny).
Cardiac action potentials
AV Node
Upstroke of the action potential in the AV node is the result of an inward Ca+ current (as in the SA node).
Conduction velocity
- reflects the time required for excitation to spread throughout cardiac tissue.
- depends on the size of the inward current during the upstroke of the action potential. The larger the inward current the higher the conduction velocity.
- is fastest in the Purkinje system.
- is slowest in the AV node, allowing time for ventricular filling before ventricular contraction. If conduction velocity through the AV node is increased, ventricular filling may be compromised.
Excitability
- is the ability of cardiac cells to initiate action potentials in response to inward, depolarizing current.
- reflects the recovery of channels that carry the inward currents for the upstroke of the action potential.
- Changes over the course of the action potential. These changes in excitability are described by refractory periods.
1. Absolute refractory period (ARP) No action potential can be initiated. (absolute means absolutely no stimulus is large enough to generate another action potential).
- Effective refractory period (ERP)
ERP is slightly longer than.
(effective means that a conducted
action potential cannot be generated). - Relative refractory period (RRP)
Action potential can be elicited but more than the usual inward current is required.
RRP begins at the end of the absolute refractory period and continues until the cell membrane has repolarized to about -70mV. During RRP it is possible to generate a second action potential (which is an abnormal configuration and shortened plateau phase).
Excitability
Absolute refractory period (ARP)
No action potential can be initiated.
(absolute means absolutely no stimulus
is large enough to generate another
action potential).
Excitability
Effective refractory period (ERP)
ERP is slightly longer than.
(effective means that a conducted
action potential cannot be generated).
Excitability
Relative refractory period (RRP)
Action potential can be elicited but more than the usual inward current is required.
RRP begins at the end of the absolute refractory period and continues until the cell membrane has repolarized to about -70mV. During RRP it is possible to generate a second action potential (which is an abnormal configuration and shortened plateau phase).
SA node
depolarization sends signal to AV node
AV node is located in right atrium intraatrial septum and intraatrial membrane
Then bundle of HIS
AKA AV bundle
becomes 2 branches
left and right branches
SA node
depolarization sends signal to AV node
AV node is located in right atrium intraatrial septum and intraatrial membrane
Then bundle of HIS
AKA AV bundle
becomes 2 branches
left and right branches
Clinical point
elevated or depressed ST segment shows positive sign for myocardial infarction
Clinical point
elevated or depressed ST segment shows positive sign for myocardial infarction
Cardiac Action Potentials
Ventricles, Atria, and the Purkinje System
Phase 0
opening of sodium channels which enters cells
leads to depolarization of atrial ventricular Purkinje fiber cells
Phase 1
potassium ions leave cells
Phase 2
during p2 opening of Ca2+ channels to enter cell
Phase 3
opening of K+ channels to leave the cell
Phase 4
K+ should reach equilibrium potential(-85mv)
Absolute refractory period
when there is second stimulus during phase 0 the cell membrane cannot accept the stimulus and it can not show any reaction to the second stimulus
Effective refractory period
when there is second stimulus during phase 1 or 2 it can accept it but cannot show any reaction
has effect but no reaction
Relative refractory period
when there is second stimulus during phase 3 the cell membrane accepted and it shows reaction to second stimulus
Absolute refractory period
when there is second stimulus during phase 0 the cell membrane cannot accept the stimulus and it can not show any reaction to the second stimulus
Effective refractory period
when there is second stimulus during phase 1 or 2 it can accept it but cannot show any reaction
has effect but no reaction
Relative refractory period
when there is second stimulus during phase 3 the cell membrane accepted and it shows reaction to second stimulus
Myocardial Cells—Nodal/Conducting Cells
The second type of cells found in the heart are nodal or conducting cells. These cells contract very weakly because they contain very few contractile elements (myofibrils).
These special cells are able to spontaneously generate action potentials without the help of nervous input like regular neurons. Along with this special property of self-excitability, they can also rapidly conduct the action potentials to atrial and ventricular muscle.
Thus, these specialized cells provide a self-excitatory system for the heart to generate impulses and a transmission system for rapid conduction of the impulses throughout the heart. Although nearly all of the cells in the heart can spontaneously generate action potentials, the sinoatrial node (or SA node) is generally the site of origin. The SA node is located in the upper posterior wall of the right atrium, and it is the first area to spontaneously depolarize, producing an action potential; this is why it is called the pacemaker of the heart.
The action potential travels through the atria to the atrial-ventricular node (AV node) and then to the Bundle of His. From the Bundle of His, the action potential travels through the Purkinje Fibers and then to the ventricular muscle.
Myocardial Cells—Conducting System of the Heart
Once the action potential is generated at the SA node, it travels throughout the heart in a highly coordinated manner. From the SA node, the action potential spreads throughout the atrial muscle, causing it to contract. From the atria, the action potential travels to the ventricles.
However, the atria are electrically isolated from the ventricles by a fibrous tissue. Therefore, the action potential cannot jump directly down to the ventricles.
The action potential must first travel through the atrio-ventricular (AV) node. Once through the AV node, the action potential travels through each branch of the Bundle of His down to the apex of the heart.
From here, the action potential propagates through the Purkinje Fibers, which rapidly distribute the action potential to the ventricular muscle which then contracts.
Myocardial tissue is full of mitochondria to produce ATP for ion pump and strong contraction
The type of junctions used are tight and gap junctions
Autonomic effects on heart rate and conduction velocity
Chronotropic effects
- produce changes in heart rate.
- A negative chronotropic effect decreases heart rate by decreasing the firing rate of the SA node.
- A positive chronotropic effect increases heart rate by increasing the firing rate of the SA node.
Dromotropic effects
- produce changes in conduction velocity, primarily in the AV node.
- dromotropic effect decreases conduction velocity through the AV node, slowing the conduction of action potentials from the atria to the ventricles and increasing the PR interval.
- A positive dromotropic effect increases conduction velocity through the AV node, speeding the conduction of action potentials from the atria to the ventricles and decreasing the PR interval.
Inotropic effects
A negative inotropic decreases force of contraction, a positive inotropic effect increases force of contraction.
Chronotropic = heartrate
Dromotropic = conduction velocity
Inotropic = contractility of myocardium
Chronotropic = heartrate
Dromotropic = conduction velocity
Inotropic = contractility of myocardium
Heart
Coronary Arteries
Sympathetic
- β1-rec: +ve Chronotropic
- β1-rec: +ve Dromotropic
- β1-rec: +ve inotropic
vasodilatation
Parasympathetic
- ve Chronotropic
- ve inotropic
- ve Dromotropic
vasoconstriction
At rest, a normal heart beats around 50 to 99 times a minute.
At rest, a normal heart beats around 50 to 99 times a minute.
Arrhythmias:
It results from abnormalities in impulse formation or in impulse conduction, Disturbances in the formation of impulses lead to change in the sinus rhythm.
Sinus tachycardia: If sinus frequency rises above 100/min (exercise, psychic excitation, fever, rise of 10 beats/min.
Sinus bradycardia: If it drops below 50-60/min.In both cases the rhythm is regular.
Arrhythmia means abnormal contraction which is not enough for ejection of large amount of blood into blood vessels
could be atrial or ventricular
Sinus tachycardia: If sinus frequency rises above 100/min (exercise, psychic excitation, fever, rise of 10 beats/min.
At rest, a normal heart beats around 50 to 99 times a minute.
Sinus tachycardia: If sinus frequency rises above 100/min (exercise, psychic excitation, fever, rise of 10 beats/min.
Sinus bradycardia: If it drops below 50-60/min.In both cases the rhythm is regular.
At rest, a normal heart beats around 50 to 99 times a minute.
Sinus bradycardia: If it drops below 50-60/min.In both cases the rhythm is regular.
Supraventricular arrhythmia due to atrial or nodal extrasystole (ES):
Abnormal or ectopic (heterotopic) impulses may arise in the atria (atrial), in the AV node (nodal) or in the ventricle (ventricular). The impulses from an atrial (or nodal) ectopic focus are transmitted to the ventricle, which thus thrown out of its sinus rhythm :supraventricular arrhythmia due to atrial or nodal extrasystole (ES).
In atrial ES the P wave is deformed but the QRS complex is normal.
In nodal extrasystole, stimulation of the atria is retrograde; the P wave is thus negative and is either masked by the QRS wave or appears shortly after it. Because in supraventricular extrasystole the sinus nodes often also depolarize.
Supraventricular arrhythmia
AKA atrial arrhythmia
when atrium receives extra signal(stimulus) from different part of ventricle which is not part of conductive system
2 factors
post myocardial infarction the healed tissue may have spontaneous depolarization which sends signal to different part of ventricle and atrium. When atrium receives that type of signal the P wave is negative on EKG
could be due to different ions such as hypercalcemia. Increased blood calcium can impact contractility of myocardium and increases the heart rate
Supraventricular arrhythmia
AKA atrial arrhythmia
when atrium receives extra signal(stimulus) from different part of ventricle which is not part of conductive system
2 factors
post myocardial infarction the healed tissue may have spontaneous depolarization which sends signal to different part of ventricle and atrium. When atrium receives that type of signal the P wave is negative on EKG
could be due to different ions such as hypercalcemia. Increased blood calcium can impact contractility of myocardium and increases the heart rate
Ventricular extrasystole (infranodal extrasystole)
Ventricular premature complexes (VPCs) are ectopic impulses originating from an area distal to the His Purkinje system. VPCs are the most common ventricular arrhythmia In this case the QRS complex of the ES is deformed.
Two common mechanisms exist for VPCs, (1) automaticity, (2) reentry, and as follows:
- Automaticity: This is the development of a new site of depolarization in nonnodal ventricular tissue, which can lead to a VPC. Increased automaticity could be due to electrolyte abnormalities or ischemic myocardium.
- Reentry circuit: Reentry typically occurs when slow-conducting tissue (eg, infarcted myocardium) is present adjacent to normal tissue. The slow-conducting tissue could be due to damaged myocardium, as in the case of a healed MI.
Ventricular extrasystole(ventricular arrythmia)
after T wave there is the QRS complex.
Premature ventricular contraction
Ischemia
hypoxemia
due to obstruction of BV which leads to deficiency of oxygen supply to tissues
Medicine side effects
long term or high dosage of medicines
Digoxin – medicine for patients with flutter/fibrillation. The medicine helps for strong contractions of ventricles and atriums. Decreases the heart rate. High dosage of this medicine can cause extracystole
Myocarditis
inflammation of myocardium
impacts the contractility of the muscle
Cardiomyopathy hypertrophic or dilated
when the muscle ventricle becomes hypertrophile(thicker) then it occupies the internal environment of the ventricle and impacts the contractility of the myocardium
Hypoxia
respiratory disorder, lung disorder, anemia, heart problem, decreased RBC, or some diseases
Hypercapnia(CO2 poisoning)
rate of CO2 is high in blood
due to
lung problems, abnormal cell respiration
tissue cannot receive sufficient amounts of oxygen for cell respiration. The heart should compensate and contract faster
Mitral valve collapse
if there is any problem with mitral valve then it impacts the contractility
Smoking, alcohol, drugs, cocaine
decreases oxygen and increases CO2 levels
Magnesium and potassium deficiency
Mg controls Calcium
deficiency of Mg can lead to hypercalcemia
K+
deficiency means failure of repolarization phase which is relaxation phase of muscle after each contraction
Calcium excess
hypercalcemia
Thyroid problems
stimulates the beta 1 adrenergic receptor and noradrenaline
beta 1 = contractility of myocardium
hyperthyroidism has palpitation and excess contractility of myocardial, heartrate, and hypertension
Heart attach
postmyocardial infarction
Premature ventricular contraction
List of possible causes:
List of possible causes:
Ischemia Certain medicines such as digoxin, which increases heart contraction Myocarditis Cardiomyopathy hypertrophic or dilated Hypoxia Hypercapnia (CO2 poisoning) Mitral valve prolapse Smoking Alcohol Drugs such as cocaine Caffeine Magnesium and potassium deficiency Calcium excess Thyroid problems Heart attack
Premature ventricular contraction
Symptoms
Symptoms
Chest pain
Faint feeling
Fatigue
Hyperventilation (after exercise)
Frequent episodes of continuous PVCs becomes a form of ventricular tachycardia (VT), which is a rapid heartbeat, because there is an extra electrical impulse, causing an extra ventricular contraction.
Treatment of Ventricular extrasystole (premature Ventricular Contraction (PVC)
PVCs can often be resolved by
- restoring the balance of magnesium, calcium and potassium within the body.
- Pharmacological agents
Class I agents
Sodium channel blockers . Class I agents are grouped by what effect they have on the Na+ channel, and what effect they have on cardiac action potentials. Lidocaine, Phenytoin.
Class II agents
Beta blockers. They act by blocking the effects of catecholamines at the β1-adrenergic receptors, thereby decreasing sympathetic activity on the heart. They decrease conduction through the AV node.
Class II agents include atenolol, propranolol, and metoprolol.
Class III
Block the potassium channels, thereby prolonging repolarization. Since these agents do not affect the sodium channel, conduction velocity is not decreased. Sotalol
Class IV agents Calcium channel blockers. They decrease conduction through the AV node, and shorten phase two (the plateau) of the cardiac action potential. They thus reduce the contractility of the heart, so may be inappropriate in heart failure. However, in contrast to beta blockers, they allow the body to retain adrenergic control of heart rate and contractility.Class IV agents include verapamil and diltiazem. ----- Know lidocaine sodium channel blocker
Know class 1 and 2 agents
Atrial Tachycardia
Atrial tachycardia is a rhythm disturbance that arises in the atria. Heart rates during atrial tachycardia are highly variable, with a range of 100-250 beats per minute (bpm). The atrial rhythm is usually regular.
Ventricular Tachycardia
It results from a rapid sequence of ectopic ventricular impulses. Beginning with ES. Ventricular filling and cardiac output decrease and ventricular fibrillation can even ensue, that is a high frequency uncoordinated twitching of the myocardium. Unless treated the failure to eject blood can be just as dangerous as cardiac arrest.with a rate between 120 and 250 beats per minute.
PR is depolarization of AV node
sometimes AV node block
First degree
a little longer then 0.2 seconds between
Second degree
multiple P between QRS
Third degree
multiple P one QRS then no more QRS
PR is depolarization of AV node
sometimes AV node block
First degree
a little longer then 0.2 seconds between
Second degree
multiple P between QRS
Third degree
multiple P one QRS then no more QRS
Av node block
PR interval in the normal heart, this time is 0.12 to 0.20 second in duration, damage to AV node causes slowing of impulse conduction and is reflected by changes in the PR interval. This condition is AV node block.
First degree AV node block
PR interval exceeds 0.20 second
Second degree AV node block
occurs when the AV node is damaged so severely that only one out of every two, three, or four atrial electrical waves can pass through to the ventricles.
ECG: P waves without associated QRS waves.
Third-degree, or complete, AV node block,
non of the atrial waves can pass through the AV node to the ventricles. Result is bradycardia.
Cardiac muscle and cardiac output
Myocardial Cells
There are two principal types of myocardial cells (myo = muscle, cardio = heart): contractile cells, which have similar features to skeletal muscle cells and nodal/conducting cells that have features similar to nerve cells.
The contractile cells of the heart contain the same contractile proteins actin and myosin arranged in bundles of myofibrils surrounded by a sarcoplasmic reticulum.
Gap junction act as channel for K, Na, Ca ions
Tight junctions
Contractile Cells
They differ from skeletal muscle by
having only one nucleus but far
more mitochondria. In fact, one-third of
their volume is taken up by mitochondria.
These cells are extremely efficient
at extracting oxygen; they extract roughly
80% of the oxygen from the passing
blood—about twice the amount of
other cells. The cells are much shorter,
are branched, and are joined together
by special structures called intercalated discs.
These structures contain tight junctions that bind the cells together, while gap junctions allow for the movement of ions and ion currents between the myocardial cells.
Because of the gap junctions, the myocardial cells of the heart can conduct action potentials from cell to cell without the need for nerves.
Steps in excitation-contraction coupling
The action potential (AP) spreads from the cell membrane into the T tubules.
During the plateau of AP, Ca2+ conductance is increased and Ca2+ enters the cell from extracellular fluid (inward Ca2+ current).
This Ca2+ entry triggers the release of even Ca2+ from the SR (Ca2+ induced Ca2+ release).
As a result of this Ca2+ release, intracellular (Ca2+) increases.
Ca2+ binds to troponin C, and tropomyosin is moved out of the way, removing the inhibition of action and myosin binding.
Actin and myosin binds, the thick and thin filaments slide past each other, and the myocardial cell contracts.
Relaxation occurs when Ca2+ is reaccumulated by the SR by an active Ca2+-ATPase pump.
Contractility
- is the intrinsic ability of the cardiac muscle to develop force at a given muscle length. It is also called inotropism.
- is related to the intracellular Ca2+ concentration.
- can be estimated by the ejection fraction (stroke volume/end-diastolic volume), which is normally 0.55 (55%).
- Positive inotropic agents produce an increase in contractility.
- Negative inotropic agents produce a decrease in contractility.
Factors that increase contractility (positive inotropism)
- Increased heart rate
- More AP occur per unit time, more Ca2+ enters the myocardial cells during the AP plateaus, more Ca2+ is released from the SR, and greater tension is produced during contraction. - Sympathetic stimulation
- Increases the inward Ca2+ current during the plateau of each cardiac action potential.
- It increases the activity of the Ca2+ pump of the SR as a result more Ca2+ is accumulated by the SR and thus more Ca2+ is available for release in subsequent beats.
3.Cardiac glycoides (digitalis)
Calcium is extremely important ion for muscle contraction
any calcium disorder either hypercalcemia or hypocalcemia can impact the muscle contraction of ventricle
The factors that increase the contractility(inotropic) of myocardium blood calcium stimulation of sympathetic system over secretion of norepinephrine digitalis(dioxine medicine)
Calcium is extremely important ion for muscle contraction
any calcium disorder either hypercalcemia or hypocalcemia can impact the muscle contraction of ventricle
The factors that increase the contractility(inotropic) of myocardium blood calcium stimulation of sympathetic system over secretion of norepinephrine digitalis(dioxine medicine)
Factors that decrease contractility (negative inotropism)
- Parasympathetic (Ach) via muscarinic receptors
- decrease the force of concentration in the atria by decreasing the inward Ca2+ current during the plateau of the cardiac action potential.
Parasympathetic, vagus nerve, and Ach
Length-tension relationship in the ventricles
- Preload
- is equivalent to end-diastolic volume, which is related to right atrial pressure.
- When venous return increases, end-diastolic volume increases and stretches or lengthens the ventricular muscle fibers. - Afterload
-for the left ventricle is equivalent to aortic pressure. Increases in aortic pressure cause an increase in afterload on the left ventricle.
-for the right ventricle is equivalent to pulmonary artery pressure.
Increases in pulmonary artery pressure cause an increase in afterload on the right ventricle. - Saromere length
- determines the maximum number of cross-bridges that can form between actin and myosin.
- determines the maximum tension, or force of contraction. - Velocity of contraction at a fixed muscle length
- Velocity of contraction is maximal when the afterload is zero.
- Velocity of contraction is decreased by increases in afterload. - Frank-Starling relationship
Preload AKA end diastolic volume
the volume of blood which exist in ventricle during relaxation phase and the pressure in ventricle
the amount of blood in each ventricle is approximately 140mL during relaxation phase(dilation phase)
Afterload
the pressure that comes to aorta or pulmonary trunk by each ventricular contraction
Frank-Starling relationship
Preload AKA end diastolic volume
the volume of blood which exist in ventricle during relaxation phase and the pressure in ventricle
the amount of blood in each ventricle is approximately 140mL during relaxation phase(dilation phase)
Afterload
the pressure that comes to aorta or pulmonary trunk by each ventricular contraction
Frank-Starling relationship
Length-tension relationship in the ventricles
Frank-Starling relationship
Describes the increases in stroke volume and cardiac output that occur in response to an increase in venous return or end-diastolic volume.
- is based on the length-tension relationship in the ventricle. Increases in end-diastolic volume cause an increase in ventricular fiber length, which produces an increase in developed tension.
- is the mechanism that matches cardiac output to venous return.
The greater the venous return, the greater the cardiac output.
- Changes in contractility shift the Frank-Starling curve upward (increased contractility) or downward (decreased contractility).
- –Increases in contractility cause an increase in cardiac output for any level of right atrial pressure or end-diastolic volume.
- –Decreases in contractility cause a decrease in cardiac output for any level of right atrial pressure or end-diastolic volume.
When length of fiber increases then the contractility of myocardium is increased
Increase VR -> up EDV -> up L/T -> up CO
Up VR -> 140ml -> up Ca2+ release from SR -> binding Ca2+ with Troponin C
because of this we have strong contraction of myocardium which increases cardiac output(CO)
When length of fiber increases then the contractility of myocardium is increased
Increase VR -> up EDV -> up L/T -> up CO
Up VR -> 140ml -> up Ca2+ release from SR -> binding Ca2+ with Troponin C
because of this we have strong contraction of myocardium which increases cardiac output(CO)
Steps in the cycle
a. 1—2 (isovolumetric contraction)
b. 2—3 (ventricular ejection)
c. 3—4 (isovolumetric relaxation)
d. 4—1 (ventricular filling)
The Cardiac Cycle
Step (1-2)—Isovolumetric ventricular contraction
(also called early ventricular systole).
This begins with the ventricles depolarizing (QRS complex) then contracting. The left ventricle is filled with blood from the left atrium and its volume is about 140 ml (end-diastolic volume). Ventricular pressure is low because the ventricular muscle is relaxed.
On excitation, the ventricle contracts and ventricular pressure increases. The mitral valve closes when left ventricular pressure is greater than left atrial pressure. Because all valves are closed, no blood can be ejected from the ventricle (isovolumetric).
The Cardiac Cycle
Step(2- 3)Ventricular systole (also called ejection period).
The aortic valve opens at point 2 when pressure in the left ventricle exceeds pressure in the aorta. Blood is ejected into the aorta, and ventricular volume decreases. The volume that is ejected in this phase is the stroke volume. The volume remaining in the left ventricle at point 3 is end-systolic volume.
The Cardiac Cycle
Step (3-4)—Early ventricular diastole (also called isovolumetric relaxation phase).
At point 3, the ventricle relaxes. When ventricular pressure decreases to less than aortic pressure, the aortic valve closes. Because all of the valves are closed again, ventricular volume is constant (isovolumetric) during this phase.
The Cardiac Cycle
Late ventricular diastole (ventricular filling).
Once left ventricular pressure decreases to less than left atrial pressure, the mitral (AV) valve opens and filling of the ventricle begins. During this phase, ventricular volume increases to about 140 ml (the end-diastolic volume).
Changes in the ventricular pressure-volume loop are caused by several factors:
a. Increased preload
- refers to an increase in end-diastolic volume and is the result of increased venous return.
- causes an increase in stroke volume based on the Frank-Starling relationship.
- The increase in stroke volume is reflected in increased width of the pressure-volume loop.
b. Increased afterload
- refers to an increase in aortic pressure.
- The ventricle must eject blood against a higher pressure, resulting in a decrease in stroke volume.
- The decrease in stroke volume is reflected in decreased width of the pressure-volume loop.
- The decrease in stroke volume results in an increase in end-systolic volume.
c. Increased contractility
- The ventricle develops greater tension than usual during systole, causing an increase in stroke volume.
- The increase in SV results in a decrease in end-systolic volume.
Stroke volume, cardiac output, and ejection fraction
- Stroke volume
- is the volume ejected from the ventricle on each beat.
Stroke volume= End-diastolic volume - End-systolic volume
- Cardiac output
CO= Stroke volume x Heart rate
- Ejection fraction
- is the fraction of the end-diastolic volume ejected in each stroke volume.
- is related to contractility.
- is normally 0.55, or 55%.
EF = Stroke volume
End-diastolic volume
Cardiac O2 consumption
- is directly related to the amount of tension developed by the ventricles.
- is increased by:
Increased afterload (increased aortic pressure)
Increased size of the heart
Increased contractility
Increased heart rate
Measurement of cardiac output by the Fick principle
CA (Cardiac output) = O2 consumption/O2 pulmonary vein-O2 pulmonary artery
Cardiac Cycle—Period of Ejection
In order for blood to be ejected from the heart, the pressure in the ventricles must be greater than the pressure in the aorta. When the pressure in the left ventricle rises above 80 mmHg (which is the pressure in the aorta), the aortic valve opens.
Immediately, blood pours out of the ventricles, while the pressure continues to increase to 120 mmHg. The period during which the ventricles empty blood into the aorta is known as the ejection period.
Heart Sounds
The opening of heart valves is a slowly developing process and produces no sound. However, when they close, the vanes of the valves and the surrounding fluid vibrate under the influence of sudden pressure differences, producing sounds that travel in all directions through the chest.
The first heart sound is produced (indirectly) by the closure of the AV valves; it is of low pitch and of relatively long duration. The second heart sound is produced (indirectly) by the closing of the aortic and pulmonary semilunar valves; this is of high pitch and of relatively smaller duration.
A third heart sound sometimes occurs in the middle of diastole. This is caused by blood flowing with rumbling motion into the almost filled ventricles; it is difficult to hear with a stethoscope.
Cardiac output
Cardiac output (CO) is the amount of blood each ventricle can pump in one minute. At rest, the cardiac output is roughly 5 liters (1.3 gallons) of blood every minute. During vigorous exercise, this can increase up to 20 l/min (5.2 gallons/min) in a normal individual and up to 35 to 40 l/min (10 gallons/min) in a highly trained athlete.
CO can be calculated using equation 5.
Heart rate (HR) is the number of times the heart beats in one minute, and stroke volume (SV) is the amount of blood pumped by one ventricle during one contraction/heartbeat.
At rest, the heart rate is 70 beats per minute (bpm) and the stroke volume is roughly 70 ml/beat. Using equation 5, a CO of roughly 5 l/min is determined. During exercise, CO increases dramatically in order to supply the working muscles with more oxygen and nutrients. This increase in CO is achieved by increasing either HR, SV, or both.
Cardiac Output
CO = (SV)(HR)
volume of blood leacing the heart/time = (amount of blood leaving the heart with ventricular contraction)(# of times the heart beats/time)
The Control of Heart Rate
The autonomic nervous system (ANS) exerts a powerful control over heart rate and force of contraction.
This is because the heart is innervated by both the parasympathetic nervous system (PSYN) and the sympathetic nervous system (SYN). The parasympathetic nerves are distributed mainly to SA and AV nodes and to a lesser extent to atrial and ventricular muscles. Sympathetic nerves are distributed to the same areas but with a stronger innervation to the ventricular muscle.
The PSYN will decrease heart rate by affecting both the SA node and AV node and will (to a lesser extent) decrease the force of contraction of the heart. The SNS, on the other hand, will have the opposite effect, increasing the heart rate and force of contraction.
If all these influences from the ANS were removed, the heart would beat at its own natural rhythm of roughly 100 bpm. Yet, the resting heart rate of a normal individual is roughly 70 bpm. Why this difference? The answer is quite interesting: in an individual at rest, there is constant activity from the PSYN keeping the heart rate slowed to roughly 70 bpm!
Atherosclerosis
Atherosclerosis is patchy intimal plaques (atheromas) in medium and large arteries; the plaques contain lipids, inflammatory cells, smooth muscle cells, and connective tissue. This disease happens when the arteries get blocked by fats and cholesterol. Atherosclerosis can affect all large and medium-sized arteries, including the coronary, carotid, and cerebral arteries, the aorta, its branches, and major arteries of the extremities
Atherosclerosis
causes, symptoms, and complications
Causes:
Dyslipidemia, diabetes, cigarette smoking, family history, sedentary lifestyle,
obesity, and hypertension
Smoking
The hallmark of atherosclerosis is the atherosclerotic plaque, which contains lipids (intracellular and extracellular cholesterol and phospholipids) inflammatory cells (eg, macrophages, T cells) smooth muscle cellsconnective tissue (eg, collagen, elastic fibers)thrombiCa++ deposits.
Symptoms:
Shortness of breath
Tightening pain in the chest
Complications:
Strokes
Damage of muscles, body organs and blood vessels
Deficiency of blood supply due to obstruction (angina)
Atherosclerosis
Pathophysiology
All stages of atherosclerosis—from initiation and growth to complication of the plaque—are considered an inflammatory response to injury. Endothelial injury is thought to have a primary role.
- Endothelial dysfunction and inhibits endothelial production of nitric oxide, a potent vasodilator and anti-inflammatory molecule.
- Such blood flow also stimulates endothelial cells to produce adhesion molecules, which recruit and bind inflammatory cells.
The net effect is endothelial binding of monocytes and T cells, migration of these cells to the subendothelial space, and initiation and perpetuation of a local vascular inflammatory response. Monocytes in the subendothelium transform into macrophages.
macrophages in the plaque produce some enzymes which digest the fibrous cap, particularly at the edges, causing the cap to thin and ultimately rupture.
Lipids in the blood, particularly low density lipoprotein (LDL) and very low density lipoprotein (VLDL), also bind to endothelial cells and are oxidized in the subendothelium.
Atrial fibrillation and flutter
Atrial fibrillation and flutter are abnormal heart rhythms in which the atria are out of sync with the ventricles.
In atrial flutter, the atria beat regularly and faster than the ventricles.
In atrial fibrillation, the heart beat is completely irregular. The atrial muscles contract very quickly and irregularly; the ventricles beat irregularly but not as fast as the atria.
When the atria fibrillate, blood that is not completely pumped out can pool and form a clot. In atrial flutter, the heart beat is usually very fast but steady. The atria beat faster than the ventricles.
Atrial fibrillation often occurs in people with various types of heart disease. Atrial fibrillation may also result from an inflammation of the heart’s covering (pericarditis), chest trauma or surgery, pulmonary disease, and certain medications
Atrial fibrillation and flutter
Causes and symptoms
In most cases, the cause of atrial fibrillation and flutter: many types of heart disease stress and anxiety caffeine alcohol tobacco diet pills open heart surgery
Heart murmurs
are generated by turbulent flow of blood, which may occur inside or outside the heart. Murmurs may be physiological (benign) or pathological (abnormal).
Abnormal murmurs can be caused by : Stenosis restricting the opening of a heart valve, causing turbulence as blood flows through it. Valve insufficiency (or regurgitation) allows backflow of blood when the incompetent valve is supposed to be closed.
ECG Electrodes
ECG standard leads
There are three standard leads, usually designated as I, II and III.
They are bipolar (i.e., they detect a change in electric potential between two points) and detect the electrical potential change in the frontal plane.
Lead I: is between the right arm and left arm electrodes, the left arm being positive.
Lead II: is between the right arm and left leg electrodes, the left leg being positive.
Lead III: is between the left arm and left leg electrodes, the left leg again being positive.
ECG Leads - Views of the Heart
Chest Electrode Placement
V1: Fourth intercostal space to the right of the sternum.
V2: Fourth intercostal space to the Left of the sternum.
V3: Directly between leads V2 and V4.
V4: Fifth intercostal space at midclavicular line.
V5: Level with V4 at left anterior axillary line.
V6: Level with V5 at left midaxillary line. (Directly under the midpoint of the armpit)
Chest Leads
a. V1 & V2
b. V3 & V4
c. V5 & V6
View
a. Right Ventricle
b. Septum/Lateral Left Ventricle
c. Anterior/Lateral Left Ventricle
Myocardial infarction
The blood supply to certain areas of the myocardium is obstructed. The muscle tissue at the center of the infarct dies off.
Causes:
In atherosclerosis, plaque builds up in the walls of your coronary arteries. This plaque is made up of cholesterol and other cells. A heart attack can occur.
Stress
Male gender
Diabetes
Family history of coronary artery disease (genetic or hereditary factors)
High blood pressure Smoking
Unhealthy cholesterol levels, especially high LDL (“bad”) cholesterol and low HDL (“good”) cholesterol.
Chronic kidney disease
Myocardial infarction
Symptoms
Chest pain (angina pectoris): Feeling the pain in only one part of your body, or it may move from your chest to your arms, shoulder, neck, teeth, jaw, belly area, or back.
The pain can be severe or mild. It can feel like:
A tight band around the chest
Bad indigestion
Something heavy sitting on your chest
Squeezing or heavy pressure
The pain usually lasts longer than 20 minutes. Rest and a medicine do not completely relieve the pain of a heart attack. Symptoms may also go away and come back.
Other symptoms of a heart attack include: Sweating Anxiety Cough Fainting Dizziness Nausea or vomiting Palpitations (feeling like your heart is beating too fast) Dyspnea
Myocardial infarction
Diagnostic criteria:
- Clinical history of ischaemic type chest pain lasting for more than 20 minutes.
- Changes in serial ECG tracings.
- Rise and fall of serum cardiac biomarkers such as creatine kinase -MB fraction and troponin T and I and myoglobin, Lactate dehydrogenase as they are more specific for myocardial injury. (The cardiac troponins T and I which are released within 4–6 hours of an attack of MI and remain elevated for up to 2 weeks).
- If there is a high positive R, there is also a Larger negative Q waves, ST segment elevation or depression, or coronary intervention are diagnostic of MI.
Management:
A MI is a medical emergency which requires immediate medical attention. Oxygen, aspirin, and nitroglycerin.
Endocarditis
Endocarditis is inflammation of the inside lining of the heart chambers and heart valves (endocardium).
Endocarditis is usually a result of a blood infection. Bacteria or other infectious substance can enter the bloodstream during certain medical procedures, including dental procedures, and travel to the heart, where it can settle on damaged heart valves. The bacteria can grow and may form infected clots that break off and travel to the brain, lungs, kidneys, or spleen.
The following increase chances for developing endocarditis:
- Artificial heart valves
- Congenital heart disease (atrial septal defect, patent ductus arteriosus)
- Heart valve problems (such as mitral insufficiency).
-History of rheumatic heart disease.
Endocarditis
Symptoms
Abnormal urine color Chills (common) Excessive sweating (common) Fatigue Fever (common) Joint pain Muscle aches and pains Night sweats Nail abnormalities (splinter hemorrhages under the nails) Paleness
Endocarditis
Test and treatment
Blood culture and sensitivity (to detect bacteria)
Chest x-ray
Complete blood count (may show mild anemia)
Echocardiogram (ultrasound of the heart)
Erythrocyte sedimentation rate (ESR)
Transesophageal echocardiogram
Treatment:
Long-term, high-dose antibiotic treatment is needed to get rid of the bacteria. Treatment is usually given for 4-6 weeks, depending on the specific type of bacteria. Blood tests will help your doctor choose the best antibiotic.
Surgery may be needed to replace damage heart valves.
Mitral stenosis
Mitral stenosis is a heart valve disorder that involves the mitral valve. Stenosis refers to a condition in which the valve does not open fully, restricting blood flow.
Causes:
the valve area becomes smaller, less blood flows to the body. The upper heart chamber swells as pressure builds up. Blood may flow back into the lungs. Fluid then collects in the lung tissue (pulmonary edema), making it hard to breathe.
- Rheumatic fever
- Congenital mitral stenosis
Mitral stenosis
symptoms and complications
Symptoms:
May begin with an episode of:
-Atrial fibrillation
-Chest discomfort (rare):
Increases with activity, decreases with rest
-Radiates to the arm, neck, jaw, or other areas Tight, crushing, pressure,
-Cough, possibly bloody (hemoptysis)
Difficulty breathing during or after exercise or when lying flat; may wake up with difficulty breathing
-Fatigue, becoming tired easily
- Bronchitis
-Palpitations
-Swelling of feet or ankles
Complications:
- Atrial fibrillation and atrial flutter
- Blood clots to the brain (stroke), intestines, kidneys, or other areas
- Heart failure
- Pulmonary edema
- Pulmonary hypertension
Mitral Stenosis (ECG)
treatment
There is atrial fibrillation. No P waves are visible. The rhythm is irregularly irregular (random).
With severe pulmonary hypertension, right ventricular hypertrophy can be seen.
Treatment:
Medical treatment includes:
-Cardiac Glycosides: These agents alter the electrophysiologic mechanisms responsible for arrhythmia.Digoxin (Lanoxin).
- Diuretics
- β-blockers
- Ca2+ channel blockers
- Anticoagulants
- balloon valvotomy
- surgical commissurotomy
- valve replacement
*Digoxin: Negatively chronotropic - i.e. slowing the heart rate by decreasing conduction of electrical impulses through the AV node, making it a commonly used antiarrhythmic agent in controlling the heart rate during atrial fibrillation or atrial flutter.
Positively inotropic - i.e. increasing the force of heart contraction via inhibition of the Na+/K+ ATPase pump.
Mitral Stenosis (ECG)
Digoxin:
Negatively chronotropic - i.e. slowing the heart rate by decreasing conduction of electrical impulses through the AV node, making it a commonly used antiarrhythmic agent in controlling the heart rate during atrial fibrillation or atrial flutter.
Positively inotropic - i.e. increasing the force of heart contraction via inhibition of the Na+/K+ ATPase pump.
Mitral regurgitation
Mitral regurgitation is a long-term disorder in which the heart’s mitral valve does not close properly, causing blood to flow backward (leak) into the upper heart chamber when the left lower heart chamber contracts. The condition is progressive, which means it gradually gets worse.
Causes:
- Mitral valve prolapse
- Congenital
- Atherosclerosis
- Endocarditis
- Heart tumors
- High blood pressure
- Marfan syndrome
- Untreated syphilis
Mitral regurgitation
Symptoms and treatment
Symptoms:
-Cough
-Fatigue
-Palpitations (related to atrial fibrillation)
-Shortness of breath during activity and when lying down
-Urination, excessive at night
enlarged liver
Treatment:
The choice of treatment depends on the symptoms present and the condition and function of the heart.
- Antibiotics reduce the risk of infective endocarditis in patients with mitral valve prolapse who are having dental work.
- Antihypertensive drugs and vasodilators.
- Anticoagulant or antiplatelet medications prevent clot formation in patients with atrial fibrillation.
- Digitalis may be used to strengthen the heartbeat, along with diuretics to remove excess fluid in the lungs.
Circuitry
Cardiac output is distributed among various organs:
Cerebral=15%
Coronary=5%
Renal=25%
Gastrointestinal=25%
Skeletal muscle=25%
Skin=5%
Regulating of arterial Pressure
Fast mechanism: neural, (baroreceptor)
Slow mechanism: hormonal (renin-angiotensin-aldosterone)
Baroreceptor reflex
- includes fast, neural mechanisms.
- is a negative feedback system that is responsible for the minute-to-minute regulation of arterial pressure.
- Baroreceptors are stretch receptors located within the walls of the carotid sinus near the bifurcation of the common carotid arteries.
Steps in the baroreceptor reflex
a. A decrease in arterial pressure decreases stretch on the walls of the carotid sinus.
- Because the baroreceptors are most sensitive to changes in arterial pressure, rapidly decreasing arterial pressure produces the greatest response.
- Additional baroreceptors in the aortic arch respond to increases, but not to decreases, in arterial pressure.
b. Decreased stretch decreases the firing rate of the carotid sinus nerve cranial nerve IX, which carries information to the vasomotor center in the brain stem.
c. The set point for mean arterial pressure in the vasomotor center is about 100 mm Hg. Therefore, if mean arterial pressure is less than 100 mm Hg, a series of autonomic responses is coordinated by the vasomotor center. These changes will attempt to increase blood pressure toward normal.
d. The responses of the vasomotor center to a decrease in mean arterial blood pressure are coordinated to increase the arterial pressure to 100 mm Hg. The responses are decreased parasympathetic (vagal) outflow to the heart and increased sympathetic outflow to the heart and blood vessels.
The following four effects attempt to increase the arterial pressure to normal:
- Increases heart rate
- Increases contractility and stroke volume
- Increases vasoconstriction of arterioles
- Increases vasoconstriction of veins
* Example of the baroreceptor reflex: response to acute blood loss
Renin-angiotensin-aldosterone system
- is a slow, hormonal mechanism.
- Regulation by adjustment of blood volume.
- Renin is an enzyme.
- Angiotensin I is inactive.
- Angiotensin II is physiologically active.
- Angiotensin II is degraded by angiotensinase.
- Example : response of the RAA system to acute blood loss.
Regulation by Aldosterone
Renin-Angiotensin-Aldosterone system
Regulation by Aldosterone
Renin-Angiotensin-Aldosterone system
Other regulation of arterial blood pressure
- Cerebral ischemia
- Chemoreceptors in the carotid and aortic bodies
- Vasaopressin (antidiuretic hormone)
- Atrial natriuretic peptide (ANP)
Other regulation of arterial blood pressure
Cerebral ischemia
a. Pco2 pressure increases in brain tissue.
b. Chemoreceptors in the vasomotor center respond by increasing sympathetic outflow to the heart and blood vessels.
Constriction of arterioles causes intense peripheral vasoconstriction and increased TPR. Blood flow to other organs (kidneys) is significantly reduced in an attempt to preserve blood flow to the brain.
c. The Cushing reaction in an example of the response to cerebral ischemia. Increases intracranial pressure cause compression of the cerebral blood vessels, leading to cerebral ischemia and increased cerebral Pco2. The vasomotor center directs an increase in sympathetic outflow to the heart and blood vessels, which causes a profound increase in arterial pressure.
Other regulation of arterial blood pressure
Chemoreceptors in the carotid and aortic bodies
- are located near the bifurcation of the common carotid arteries and along the aortic arch.
- have very high rates of O2 consumption and are very sensitive to decreases in the partial pressure of oxygen (Po2).
- Decreases in Po2 activate vasomotor centers that produce vasoconstriction, an increase in TPR, and an increase in arterial pressure.
Other regulation of arterial blood pressure
Regulation by Antidiuretic hormone( ADH)
too little water in blood -> detected by hypothalamus -> more ADH secreted into blood by pituitary gland -> kidneys absorb less water from blood -> less urine produced -> blood water level back to normal
too much water in blood -> detected by hypothalamus -> less ADH secreted into blood by pituitary gland -> kidneys absorb more water from blood -> lots of dilute urine produced -> blood water level back to normal
Other regulation of arterial blood pressure
Atrial Natriuretic peptide
Physiological effects
ANP binds to a specific set of receptors. Receptor-agonist binding causes a reduction in blood volume and therefore a reduction in cardiac output and systemic blood pressure.
- Inhibits renin secretion, thereby inhibiting the renin-angiotensin system.
- Reduces aldosterone secretion by the adrenal cortex.
- Relaxes vascular smooth muscle in arterioles and venules.
Microcirculation and lymph
Structure of capillary beds
- At the junction of the arterioles and capillaries is a smooth muscle band called the precapillary sphincter.
- True capillaries do not have smooth muscle; they consist of a single layer of endothelial cells surrounded by a basement membrane.
- Clefts (pores) between the endothelial cells allow passage of water-soluble substances. The clefts represent a very small fraction of the surface area (<0.1%).
- Blood flow through the capillaries is regulated by contraction and relaxation of the arterioles and the precapillary sphincters.
Passage of substances across the capillary wall
- Lipid-soluble substances (o2 and CO2)
- Small water-soluble substance
- cross via the water-filled clefts between the endothelial cells.
- include water, Glucose, and amino acid.
- Proteins molecules are too large to pass freely through the clefts.
- In the brain, the clefts between endothelial cells are exceptionally tight (blood-brain barrier).
- In the liver and intestine, the clefts are exceptionally wide and allow passage of protein. These capillaries are called sinusoids. - Large water-soluble substances
- can cross by pinocytosis.
Lymph
Function of lymph
a. Normally, filtration of fluid out of the capillaries is slightly greater than absorption of fluid into the capillaries. The excess filtered fluid is returned to the circulation via the lymph.
Lymph also returns any filtered protein to the circulation.
b. Unidirectional flow of lymph
- one-way flap valves permit interstitial to enter, but not leave, the lymph vessels.
- Flow through larger lymphatic vessels is also unidirectional, and is aided by one-way valves and skeletal muscle contraction.
c. Edema
- occurs when the volume of interstitial fluid exceeds the capacity of the lymphatic to return it to the circulation.
- can be caused by excess filtration or blocked lymphatics.
Kidney:
It maintains constancy of ECF volume and of osmolality by balancing intake and excretion of Na+ and water.
Furthermore, the kidney achieves constancy of extracellular K+ concentration and of blood and cellular PH by adjusting excretion of H+ and HCO3- .
It conserves nutrients (e.g. glucose, aminoacids) and excretes end products of metabolism (urea, uric acid).
It also has numerous metabolic functions (arginine formation, gluconeogenesis, peptide hydrolysis).
It is a source of hormones (angiotensin II, erythropoietin, prostaglandins)
Kidney:
reabsorption, excretion, and secretion
*** Reabsorption: Whence the greater part of this ultrafiltrate is transported across the tubule wall and reenters the blood.
*** Excretion: The fraction that is not reabsorbed remains in the tubules and appears in the terminal urine.
*** Secretion: Some urinary solvents enter the nephron lumen from tubule cells by secretion.
Kidney
- Medulla
- Cortex
Nephron:
- A nephron consists of a glomerulus and renal tubule.
1. The glomerulus is a glomerular capillary network, which emerges from an afferent arteriole.
- Renal tubule comprises the following segments:
- Proximal tubule
- Loop of Henle (thin decending limb, a thin ascending and a thick ascending limb)
- Distal tubule
- Collecting ducts.
The nephron tubule and renal vasculature
Blood enters each kidney via renal artery, which branches into interlobar a., arcuate a. and cortical radial .
The smallest arteries subdivide into first set of arterioles, the afferent arterioles. The afferent arterioles deliver blood to the first capillary network, the glomerular capillaries.
Then blood leaves the glomerular capillaries, via a second set of arterioles, the efferent arterioles, which deliver blood to a second capillary network, the peritubular capillaries. The peritubular capillaries surround the nephrons. Solutes and water are reabsorbed into the peritubular capillaries and a few solutes are secreted from the peritubular capillaries. Blood from the peritubular capillaries flows into small veins and then into the renal vein.
In the juxtamedullary nephrons, the peritubular capillaries have a specialization called the vasa recta. Vasa recta serve as osmotic exchangers for the production of concentrated urine.
(a=artery)
Body Fluids
- Total body water (TBW) is approximately 60% of body weight.
- The percentage of TBW is highest in newborns and adult males and lowest in adult females and in adults with a large amount of adipose tissue.
Distribution fluid
- Plasma is ¼ of the ECF.
- Interstitial fluid is ¾ of the ECF.
60-40-20 rule:
- TBW is 60% of body weight.
- ICF is 40% of body weight
- ECF is 20% of body weight
Glomerular filtration
The glomerular capillaries have large pores in their walls, and the layer of Bowman’s capsule in contact with the glomerulus has filtration slits. Water, together with dissolved solutes (but not proteins) can thus pass from the blood plasma to the inside of the capsule and the nephron tubules.
The volume of this filtrate produced by both kidneys per minute is called the glomerular filtration rate (GFR).
Glomerular ultrafiltrate
The fluid that enters the glomerular capsule is called ultrafiltrate. Because glomerular capillaries are extremely permeable and have an extensive surface area, this modest net filtration pressure produces an extraordinarily large volume of filtrate. The glomerular filtration rate (GFR) is the volume of filtrate produced by both kidneys per min.
The GFR averages 115 ml per min in woman and 125 ml per min in men. It 180 L per day. Most of the filtered water must obviously be returned immediately to the vascular system, or a person would literally urinate to death within minutes.
Glomerular Filtration Rate (GFR)
Measurement of GFR-clearance of inulin-Inulin is filtered, but not reabsorbed or secreted by the renal tubules.
GFR= U inulin V/ P inulin
U=Urine concentration of inulin (mg/ml)
P=Plasma concentration of inulin (mg/ml)
Renal Clearance
Clearance equation
- indicates the volume of plasma cleared of a substance per unit time.
- The units of clearance are ml/min and ml/24hr.
C=UV/P
C=clearance (ml/min or ml/24hr)
U= urine concentration (mg/ml)
V=urine volume/time (ml/min)
P-plasma concentration (mg/ml)
Reabsorption and secretion
Reabsorption of glucose
a. Na+-glucose cotransport in the proximal tubule reabsorbs glucose from tubular fluid into the blood. There are a limited number of Na+-glucose carriers.
b. At plasma glucose concentrations less than 250 mg/dl, all of the filtered glucose can be reabsorbed because plenty of carriers are available; in this range, the line for reabsorption is the same as that for filtration.
c. At plasma glucose concentration greater than 350 mg/dl, the carriers are saturated. Therefore, increases in plasma concentration above350 mg/dl do not result in increased rates of reabsorption. The reabsorptive rate at which the carrires are saturated is the transport maximum ™.
Reabsorption and secretion
Excretion of glucose
a. At plasma concentrations less than 250 mg/dl, all of the filtered glucose is reabsorbed and excretion is zero. Threshold is approximately 250mg/dl.
b. At plasma concentrations greater than 350 mg/dl, reabsorption is saturated ™. Therefore, as the plasma concentration increases, the additional filtered glucose cannot be reabsorbed and is excretes in the urine.
NaCl Regulation
General information about Na+ reabsorption
- Na+ is filtered across the glomerular capillaries; therefore, the Na+ in the tubular fluid of Bowman’s space equals that in plasma
- Na+ is rabsorbed along the entire nephron, and very little is excreted in urine <1% of the filtered load.
Na+ reabsorption along the nephrone
- Proximal tubule
- reabsorb 2/3, or 67%, of the filtered Na+ and H2O, more than any other part of the nephron.
- is the site of glumerulo-tubular balance.
- The reabsorption of Na+ and H2O in the proximal tubule are exactly proportional.
Early proximal tubule-special features
- reabsorbs Na+ and H2O with HCO3-, glucose, amino acids, phosphate, and lactate.
- Na+ is reabsorbed by cotransport with glucose, AAs, phosphate, and lactate. These cotransport processes account for the reabsorption of all of the filtered glucose and AAs.
- Na+ is also reabsorbed by countertransport via Na+-H+ exchange, which is linked directly to the reabsorption of filtered HCO3-.
Middle and late proximal tubules-special features
- Filtered glucose, amino acids, and HCO3- have already been completely removed from the tubular fluid by reabsorption in the early proximal tubule.
- In the middle and late proximal tubules, Na+ is reabsorbed with Cl-.
Thick ascending limb of the loop of Henle
- reabsorbs 25% of the filtered Na+.
- contains a Na+-K+-2Cl- cotransporter in the luminal membrane.
- is impermeable to water. NaCl is reabsorbed without water. As a result, tubular fluid Na+ and tubular fluid osmolarity decrease to less than their concentrations in plasma This segment, therefore, is called the diluting segment.
Distal tubule and collecting duct
- together reabsorb 8% of the filtered Na+.
a. Early distal tubule-special features. - reabsorbs NaCl by a Na+-Cl- cotransporter.
- is impermeable to water.
- is called the cortical diluting segment.
Late distal tubule and collecting duct-special features
- Principal cells
- reabsorb Na+ and H2O.
- secrete K+.
- Aldosterone increases Na+ reabsorption and increases K+ secretion.
- Antidiuretic Hormone increases H2O permeability by directing the in secretion of H2O channels in the luminal membrane.
In the absence of ADH, the principal cells are virtually impermeable to water.
Late distal tubule and collecting duct-special features
- alpha Intercalated cells
- secrete H+ by a H+ adenosine triphosphatase (ATP ase), which is stimulated by aldosterone.
- reabsorb K+ by a H+, K+-ATPase.
K+ Regulation
Shifts of K+ between the ICF and ECF
- Most of the body’s K+ is located in the ICF.
- A shift of K+ out of cells causes hyperkalemia.
- A shift of K+ into cells causes hypokalemia.
K+ Regulation
Renal regulation of K+ balance
- K+ is filtered, reabsorbed, and secreted by the nephron.
- K+ balance is achieved when urinary excretion of K+ exactly equals intake of K+ in the diet.
- K+ excretion can vary widely from 1% to 110% of the filtered load, depending on dietary K+ intake, aldosterone levels, and acid-base status.
K+ Regulation
Glumerular capillaries
-Filtration occurs freely across the glomerular capillaries.
K+ Regulation
Proximal tubule
reabsorbs 67% of the filtered K+ along with Na+ and H2O.
K+ Regulation
Thick ascending limb of the loop of henle
-reabsorbs 20% of the filtered K+.
Reabsorption involves the Na+-K+-2Cl- cotransporter in the luminal membrane of cells in the thick ascending limb.
K+ Regulation
Distal tubule and collecting duct
either reabsorb or secrete K+, depending on dietary K+ intake.
Secretion of K+
- occurs in the principal cell.
- is variable and accounts for the wide range of urinary K+ excretion.
- depends on factors such as dietary K+, aldosterone levels, acid-base status, and urine flow rate.
Dietary K+
- A diet high in K+ increases K+ secretion, and a diet low in K+ decreases K+ secretion.
- On a high-K+ diet, intracellular K+ increases so than the driving force for K+ secretion also increases.
- On a low-K+ diet, intracellular K+ decreases so that the driving force for K+ secretion decreases.
Also, the alpha-intercalated cells are stimulated to reabsorb K+ by the H+, K+-ATPase.
Aldosterone
- increases K+ secretion.
- The mechanism involves increased Na+ entry into the cells across the luminal membrane and increased pumping of Na+ out of the cells by the Na+-K+ pump. Stimulation of the Na+-K+ pump simultaneously increases K+ uptake into the principal cells, increasing the intracellular K+ concentration and the driving force for K+ secretion. Aldosterone also increases the number of luminal membrane K+ channels.
- Hyperaldosteronism increases K+ secretion and causes hypokalemia.
- Hypoaldosteronism decreases K+ secretion and causes hyperkalemia.
Acid-base
- Effectively, H+ and K+ exchange for each other across the basolateral cell membrane.
- Acidosis decreases K+ secretion,. The blood contains excess H+; therefore, H+ enters the cell across the basolateral membrane and K+ leaves the cell. As a result, the intracellular K+ concentration and the driving force for K+ secretion decrease.
- Alkalosis increases K+ secretion. The blood contains too little H+; therefore, H+ leaves the cell across the basolateral membrane and K+ enters the cell. As a result, the intracellular K+ concentration and driving force for K+ secretion increase.
Renal Regulation of Urea, Phosphate, Calcium, and Magnesium
Urea
-Fifty percent of the filtered urea is reabsorbed passively in the proximal tubule.
Rest are impermeable.
-ADH increases the urea permeability of the inner medullary collecting ducts.
Renal Regulation of Urea, Phosphate, Calcium, and Magnesium
Phosphate
- Eighty-five percent of the filtered phosphate is reabsorbed in the proximal tubule by Na+-phosphate cotransport. 15% of the filtered load is excreted in urine.
- Parathyroid hormone inhibits phosphate reabsorption in the proximal tubule by activating adenylate cyclase, PTH causes phosphaturia and increased urinary cAMP.
Renal Regulation of Urea, Phosphate, Calcium, and Magnesium
Calcium
- Sixty percent of the plasma Ca+ is filtered across the glomerular capillaries.
- Together, the proximal tubule and thick ascending limb reabsorb more than 90% of the filtered Ca+ by passive processes that are coupled to Na+ rabsorption.
- Together, the distal tubule and collecting duct reabsorb 8% of the filtered Ca+ by an active process.
- PTH increases Ca+ reabsorption by activating adenylate cyclase in the distal tubule.
Renal Regulation of Urea, Phosphate, Calcium, and Magnesium
Magnesium
- is reabsorbed in the proximal tubule, thick ascending limb of the loop of Henle, and distal tubule.
- In the thick ascending limb, Mg2+ and Ca+ compete for reabsorption; therefore, hypercalcemia causes an increase in Mg2+ excretion (by inhibiting Mg+ reabsorption ).
Production of concentrated urine
- is also called hyperosmotic urine, in which urine osmolarity> blood osmolarity.
- is produced when circulating ADH levels are high (e.g., water deprivation, hemorrhage, SIADH).
Production of concentrated urine
Corticopapillary osmotic gradient-high ADH
- is the gradient of osmolarity from the cortex (300mOsm/L to the papilla (1200mOsm/L), and is composed primarily of NaCl and urea.
- is established by countercurrent multiplication and urea recycling.
- is maintained by countercurrent exchange in the vasa recta.
Production of concentrated urine
Proximal tubule-high ADH
- The osmolarity of the glomerular filtrate is identical to that of plasma (300mOsm/L).
- Two-thirds of the filtered H2O is reabsorbed isosmotically (with Na+, Cl-, HCO3-. Glucose, AAs, ) in the proximal tubule.
TF/P osm= 1.0 throughout the proximal tubule because H2O is reabsorbed isosmotically with solute.
Production of concentrated urine
Thick ascending limb of the loop of Henle-high ADH
- is called the diluting segment.
- reabsobs NaCl by the Na+-K+-2Cl- cotransporter.
- is impermeable to H2O. Therefore, H2O is not reabsorbed with NaCl, and the tubular fluid becomes dilute.
- The fluid that leaves the thick ascending limb has an osmolarity of 100 mOsm/L and TF/P osm<1.0 as a result of the dilution process.
Production of concentrated urine
Early distal tubule-high ADH
- is called the cortical diluting segment.
- like the thick ascending limb, the early distal tubule reabsorbs NaCl but is impermeable to water. Consequently, tubular fluid is further diluted.
Production of concentrated urine
Late distal tubule-high ADH
- ADH increases the H2O permeability of the principal cells of the late distal tubule.
- H2O is reabsorbed from the tubule until the osmolarity of distal tubular fluid equals that of the surrounding interstitial fluid in the renal cortex (300mOsm/L)
- TF/Posm=1.0 at the end of the distal tubule because osmotic equilibration occurs in the presence of ADH.
Production of concentrated urine
Collecting ducts-High ADH
- as in the late distal tubule, ADH increases the H2O permeability of the principal cells of the collecting ducts.
- As tubular fluid flows through the collecting ducts, it passes through the corticopapillary gradient (regions of increasingly higher osmolarity), which was previously established by counterrecurrent multiplication and urea recycling.
- H2O is reabsorbed from the collecting ducts until the osmolarity of tubular fluid equals that the surrounding interstitial fluid.
- The osmolarity of the final urine equals that at the bend of the loop of Henle (1200mOsm/L)
Glomerulonephritis
Glomerulonephritis (nephritic syndrome) is a disorder of glomeruli. It is characterized by body tissue swelling (edema), high blood pressure, and the presence of red blood cells in the urine.
Glomerulonephritis
Causes
Glomerulonephritis can be:
Primary, affecting only the kidneys,
Secondary, caused by a vast array of disorders that affect other parts of the body.
Glomerulonephritis
Causes:
Acute Glomerulonephritis:
Acute glomerulonephritis most often occurs as a complication of throat or skin infection by streptococcus, a type of bacteria. Acute glomerulonephritis that occurs after a streptococcal infection (post-streptococcal glomerulonephritis).
Infections with other types of bacteria, such as
-staphylococcus and pneumococcus,
-viral infections, such as chickenpox,
-parasitic infections, such as malaria.
-Noninfectious causes of acute glomerulonephritis include:
-membranoproliferative glomerulonephritis,
-immunoglobulin A (IgA) nephropathy,
-systemic lupus erythematosus (lupus),
Acute glomerulonephritis that develops into rapidly progressive glomerulonephritis most often results from conditions that involve an abnormal immune reaction.
Glomerulonephritis
Chronic Glomerulonephritis:
Occasionally, chronic glomerulonephritis is caused by hereditary nephritis, an inherited genetic disorder. In many people, the cause of chronic glomerulonephritis cannot be identified.
Glomerulonephritis
Symptoms
-Edema: Puffiness of the face Eyelids but later is prominent in the legs. -Blood pressure -headaches -visual disturbances -coma -nausea -general feeling of illness (malaise) -weakness, fatigue -fever -Loss of appetite, nausea, vomiting -abdominal pain -joint pain
Glomerulonephritis
Treatment
Following a diet that is low in protein and sodium may be necessary until kidney function recovers.
- Diuretics may be prescribed to help the kidneys excrete excess sodium and water.
- High blood pressure needs to be treated. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs).
- When a bacterial infection is suspected as the cause of acute glomerulonephritis, antibiotics.
- Restricting the amount of protein in the diet is modestly helpful in reducing the rate of kidney deterioration.
- End-stage kidney failure can be treated with dialysis or a kidney transplant.
Pyelonephritis
Pyelonephritis is a bacterial infection (90% is by Escherichia Coli) of one or both kidneys.
Infection can spread up the urinary tract to the kidneys, or the kidneys may become infected through bacteria in the bloodstream.
Symptoms:
Chills, fever, back pain, nausea, and vomiting can occur.
Urine and sometimes blood tests are done to diagnose pyelonephritis.
Treatment:
Antibiotics are given to treat the infection.
Stones in the Urinary Tract
Stones (calculi) are hard masses that form anywhere in the urinary tract and may cause pain, bleeding, obstruction of the flow of urine, or an infection.
Causes
Stones may form because the urine becomes too saturated with salts that can form stones or because the urine lacks the normal inhibitors of stone formation. Citrate is such an inhibitor.
About 80% of the stones are composed of calcium, and the remainder are composed of various substances, including uric acid, cystine.
Stones are more common in people with hyperparathyroidism.
Stones in the Urinary Tract
Treatment
Small stones that are not causing symptoms, obstruction, or an infection usually do not need to be treated.
- Drinking plenty of fluids has been recommended to help stones pass, but it is not clear that this approach is helpful.
- Drugs that may help the stone pass include alpha-adrenergic blockers (such as tamsulosin).
- Potassium citrate
- Calcium channel blockers (such as Verapamil)
Once a stone has passed, no other immediate treatment is needed.
-The pain of renal colic may be relieved with nonsteroidal anti-inflammatory drugs (NSAIDs) or opioids.
Acid-Base Balance
Volatile acid
Two types of acid are produced in the body(Volatile acid and Nonvolatile acid)
- is CO2.
- is produced from the aerobic metabolism of cells.
- CO2 combines with H2O to form the weak acid H2CO3 which dissociates
into H+ and HCO3 by the following reactions
-Carbonic anhydrase, which is present in most cells, catalyzes the reversible reaction between CO2 and H2O.
Acid-Base Balance
Nonvolatile acids
Two types of acid are produced in the body(Volatile acid and Nonvolatile acid)
- are also called fixed acids.
- include sulfuric acid H2SO4 (a product of protein catabolism) and phosphoric acid (a product of phospholipid catabolism)
- are normally produced at a rate of 40-60mmoles/day.
- other fixed acids that may be overproduced in disease or may be ingested include ketoacids, lactic acid, and salicylic acids.
Buffers
Extracellular buffers
- prevent a change in pH when H+ ions are added to or removed from a solution.
- are most effective within 1.0 pH unit of the pK of the buffer.
a. The major extracellular buffer is HCO3-, which is produced from CO2 and H2O.
b. Phosphate is a minor extracellular buffer.
- Phosphate is most important as a urinary buffer; excretion of H+ as H2PO4- is called titratable acid.
Buffers
Intracellular buffers
- prevent a change in pH when H+ ions are added to or removed from a solution.
- are most effective within 1.0 pH unit of the pK of the buffer.
a. Organic phosphates
b. Proteins
- Hemoglobin is a major intracellular buffer.-In the physiologic pH range, deoxyhemoglobin is a better buffer than oxyhemoglobin.
Renal acid-base
Reabsorption of filtered HCO3-
-occurs primarily in the proximal tubule.
A. Key features of reabsorption of filtered HCO3-
1. H+ and HCO3- are produced in the proximal tubule cells from CO2 and H2O. CO2 and H2O combine to form H2CO3 Carbonic acid , catalyzed by intracellular carbonic anhydrase; H2CO3 dissociates into H+ and HCO3-. H+ is secreted into the lumen via the Na+-H+ exchange mechanism in the luminal membrane. The HCO3- is reabsorbed.
- In the lumen, the secreted H+ combines with filtered HCO3- to form H2CO3, which dissociates into CO2 and H2O, catalyzed by brush border carbonic anhydrase. CO2 and H2O diffuse into the cell to start the cycle again.
- The process results in net reabsorption of filtered HCO3-. However, it does not result in net secretion of H+.
Regulation of reabsorption of filtered HCO3-
Filtered load
-Increases in the filtered load of HCO3- result in increased rates of HCO3- reabsorption. However, in the plasma HCO3- concentration becomes very high (metabolic alkalosis), the filtered load will exceed the reabsorptive capacity, and HCO3- will be excreted in the urine.
Regulation of reabsorption of filtered HCO3-
Pco2
- Increases in Pco2 result in increased rates of HCO3- reabsorption because the supply of intracellular H+ for secretion is increased.
- Decreases in Pco2 result in decreased rates of HCO3- reabsorption because the supply of intracellular H+ for secretion is decreased.
- These effects of changes in Pco2 are the physiologic basis for the renal compensation for respiratory acidosis and alkalosis
Regulation of reabsorption of filtered HCO3-
ECF volume
- ECF volume expansion results in decreased HCO3- reabsorption.
- ECF volume concentration results in increased HCO3- reabsorption (contraction alkalosis)
Regulation of reabsorption of filtered HCO3-
Angiotensin II
stimulates Na+-H+ exchange and thus increases HCO3- reabsorption, contributing to the contraction alkalosis that occurs secondary to ECF volume contraction.
Excretion of fixed H+
-Fixed H+ produced from the catabolism of protein and phospholipid is excreted by two mechanisms, titratable acid and NH4+.
Excretion of H+ as titratable acid (H2PO4)
- the amount of H+ excreted as titratable acid depends on the amount of urinary buffer present and the pK of the buffer.
1. H+ and HCO3- are produced in the cell from CO2 and H2O. The H+ is secreted into the lumen by an H+-ATPase, and the HCO3- is reabsorbed into the blood (new HCO3). In the urine, the secreted H+ combines with filtered HPO4-2 to form H2PO4-, which is excreted as titratable acid.
2. This process results in net secretion of H+ and net reabsorption of newly synthesized HCO3-.
3. As a result of H+ secretion, the pH of urine becomes progressively lower. The minimum urinary pH is 4.4.
4. The amount of H+ excreted as titratable acid is determined by the amount of urinary buffer and the pK of the buffer.
Acid-base disorders
Metabolic acidosis
A. Overproduction or ingestion of fixed acid or loss of base produces an increase In arterial (H+) (acidemia).
B. HCO3- is used to buffer the extra fixed acid. As a result, the arterial (HCO3) decreases. This decrease in the primary disturbance.
C. Acidemia causes hyperventilation (Kussmaul breathing), which is the respiratory compensation for metabolic acidosis.
D. Renal correction of metabolic acidosis consists of increased excretion of the excess fixed H+ as titratable acid and NH4+, and increased reabsorption of new HCO3-, which replenishes the HCO3- used in buffering the added fixed H+.
-In chorionic metabolic acidosis, an adaptive increase in NH3 ammonia synthesis aids in the excretion of excess H+.
Acid-base disorders
Metabolic alkalosis
A. Loss of fixed H+ or gain of base produces a decrease in arterial H+ (alkalemia)
b. As a result, arterial HCO3- increases. This increase is the primary disturbance.
- For example, in vomiting H+ is lost from the stomach, HCO3- remains behind in the blood, and the HCO3- increases.
C. Alkalemia causes hypoventilation, which is the respiratory compensation for metabolic alkalosis.
D. Renal correction of metabolic alkalosis consists of increased excretion of HCO3- because the filtered load of HCO3- exceeds the ability of the renal tubule to reabsorb it.
-If metabolic alkalosis is accompanied by ECF volume contraction (vomiting), the reabsorption of HCO3- increases (secondary to ECF volume contraction), worsening the metabolic alkalosis.
