Systemic and Special Circulations

Overview of Systemic Circulation and Capillary Exchange

Anatomy review of systemic and pulmonary circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment

Blood flows through the heart and lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy in one direction, sequentially through the following structures: 

• Deoxygenated blood enters the heart via the superior vena cava Superior vena cava The venous trunk which returns blood from the head, neck, upper extremities and chest. Mediastinum and Great Vessels: Anatomy (SVC) and the inferior vena cava Inferior vena cava The venous trunk which receives blood from the lower extremities and from the pelvic and abdominal organs. Mediastinum and Great Vessels: Anatomy ( IVC IVC The venous trunk which receives blood from the lower extremities and from the pelvic and abdominal organs. Mediastinum and Great Vessels: Anatomy) → 
• Right atrium (RA) → tricuspid valve Tricuspid valve The valve consisting of three cusps situated between the right atrium and right ventricle of the heart. Heart: Anatomy → right ventricle (RV) → pulmonary valve Pulmonary valve A valve situated at the entrance to the pulmonary trunk from the right ventricle. Heart: Anatomy → 
• Pulmonary trunk Pulmonary Trunk Truncus Arteriosus → pulmonary arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology → lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy:
  • Thin-walled capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries: Histology allows gas exchange Gas exchange Human cells are primarily reliant on aerobic metabolism. The respiratory system is involved in pulmonary ventilation and external respiration, while the circulatory system is responsible for transport and internal respiration. Pulmonary ventilation (breathing) represents movement of air into and out of the lungs. External respiration, or gas exchange, is represented by the O2 and CO2 exchange between the lungs and the blood. Gas Exchange → oxygenation of blood
  • Very-low-pressure system
  • Oncotic pressure Oncotic Pressure Edema in the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy > hydrostatic pressure Hydrostatic pressure The pressure due to the weight of fluid. Edema
    • strongly favors absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption of fluid (prevents fluid accumulation in the alveolar walls and lumens, which would impede gas exchange Gas exchange Human cells are primarily reliant on aerobic metabolism. The respiratory system is involved in pulmonary ventilation and external respiration, while the circulatory system is responsible for transport and internal respiration. Pulmonary ventilation (breathing) represents movement of air into and out of the lungs. External respiration, or gas exchange, is represented by the O2 and CO2 exchange between the lungs and the blood. Gas Exchange)
    • Clinical relevance: ↑ left-sided heart pressures (e.g., mitral valve Mitral valve The valve between the left atrium and left ventricle of the heart. Heart: Anatomy stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS)) may increase pulmonary pressures and lead to pulmonary edema Pulmonary edema Pulmonary edema is a condition caused by excess fluid within the lung parenchyma and alveoli as a consequence of a disease process. Based on etiology, pulmonary edema is classified as cardiogenic or noncardiogenic. Patients may present with progressive dyspnea, orthopnea, cough, or respiratory failure. Pulmonary Edema and hypoxia Hypoxia Sub-optimal oxygen levels in the ambient air of living organisms. Ischemic Cell Damage.
• Pulmonary veins Pulmonary veins The veins that return the oxygenated blood from the lungs to the left atrium of the heart. Lungs: Anatomy → left atrium (LA) → mitral valve Mitral valve The valve between the left atrium and left ventricle of the heart. Heart: Anatomy → left ventricle (LV) → aortic valve Aortic valve The valve between the left ventricle and the ascending aorta which prevents backflow into the left ventricle. Heart: Anatomy → 
• Aorta Aorta The main trunk of the systemic arteries. Mediastinum and Great Vessels: Anatomy → systemic arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology → capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries: Histology (blood is deoxygenated) → veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology → SVC/ IVC IVC The venous trunk which receives blood from the lower extremities and from the pelvic and abdominal organs. Mediastinum and Great Vessels: Anatomy → back to the heart

Distribution of blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure

• At rest, the majority of cardiac output Cardiac output The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). Cardiac Mechanics flows to:
  • Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy: approximately 25%
  • Kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy: approximately 20%
  • Skeletal muscle: approximately 20%
  • Brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification: approximately 15%
• Vascular beds Vascular beds Gas Exchange receive 5%–10% of blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure:
  • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions: approximately 7%
  • Intestines: approximately 5%
  • Heart: approximately 5%
• Other vascular beds Vascular beds Gas Exchange: approximately 3%
• Vascular beds Vascular beds Gas Exchange can increase their blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure through vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs (some organs much more so than others)
  • Skeletal muscle: can substantially ↑ blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure through vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs
  • Heart: has the lowest ability to ↑ blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure 
  • Brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification: although it has the ability to increase flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure, of all the organs, keeps flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure the most constant

Blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure through and around capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries: Histology

• Blood enters the capillary beds Capillary beds Groups of 10–100 individual capillary vessels supplied by a single metarteriole. Capillaries: Histology through the arterioles Arterioles The smallest divisions of the arteries located between the muscular arteries and the capillaries. Arteries: Histology → metarterioles Metarterioles Short vessels linking arterioles and capillaries. Arteries: Histology → capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries: Histology
• Blood drains into the thoroughfare channel Thoroughfare Channel Capillaries: Histology → empties into venules Venules The minute vessels that collect blood from the capillary plexuses and join together to form veins. Veins: Histology
• Metarterioles Metarterioles Short vessels linking arterioles and capillaries. Arteries: Histology contain smooth muscle precapillary sphincters Precapillary Sphincters Capillaries: Histology at the entrance to each individual capillary:
  • Regulates the amount of blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure into the capillary bed
  • When sphincters are closed, blood bypasses the capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries: Histology and flows straight through the thoroughfare channel Thoroughfare Channel Capillaries: Histology.
• Arteriovenous anastomoses Arteriovenous anastomoses A vessel that directly interconnects an artery and a vein, and that acts as a shunt to bypass the capillary beds. Not to be confused with surgical anastomosis or arteriovenous fistula. Capillaries: Histology (AV shunts): vessels that bypass the capillary beds Capillary beds Groups of 10–100 individual capillary vessels supplied by a single metarteriole. Capillaries: Histology and directly connect arteries and veins Arteries And Veins ACES and RUSH: Resuscitation Ultrasound Protocols
  • AV shunts are present when precapillary sphincters Precapillary Sphincters Capillaries: Histology are closed.
  • Numerous in the dermis Dermis A layer of vascularized connective tissue underneath the epidermis. The surface of the dermis contains innervated papillae. Embedded in or beneath the dermis are sweat glands; hair follicles; and sebaceous glands. Skin: Structure and Functions: help regulate body heat Heat Inflammation

Physiology of capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries: Histology

Functions:

• Gas exchange Gas exchange Human cells are primarily reliant on aerobic metabolism. The respiratory system is involved in pulmonary ventilation and external respiration, while the circulatory system is responsible for transport and internal respiration. Pulmonary ventilation (breathing) represents movement of air into and out of the lungs. External respiration, or gas exchange, is represented by the O2 and CO2 exchange between the lungs and the blood. Gas Exchange:
  • O₂ leaves the RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology.
  • CO₂ enters the RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology.
• Nutrient delivery
• Blood picks up cellular and interstitial waste.

Starling forces Starling Forces Capillaries: Histology applied to capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries: Histology:

• Relatively higher hydrostatic pressure Hydrostatic pressure The pressure due to the weight of fluid. Edema in the arterioles Arterioles The smallest divisions of the arteries located between the muscular arteries and the capillaries. Arteries: Histology pushes fluid, nutrients, and other cellular material into the surrounding extracellular fluid Extracellular fluid The fluid of the body that is outside of cells. It is the external environment for the cells. Body Fluid Compartments (ECF).
• Plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis generally cannot pass through the capillary walls → plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products oncotic pressure Oncotic Pressure Edema ↑ toward the venous end of the capillary
• Relatively higher oncotic pressure Oncotic Pressure Edema in the venules Venules The minute vessels that collect blood from the capillary plexuses and join together to form veins. Veins: Histology allow waste to be absorbed into the vessels.

Clinical relevance of increased hydrostatic pressure Hydrostatic pressure The pressure due to the weight of fluid. Edema within capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries: Histology:

• Any condition that prevents blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure from moving forward on the venous side can lead to an increase in hydrostatic pressure Hydrostatic pressure The pressure due to the weight of fluid. Edema within the capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries: Histology, which will result in more fluid and substrate Substrate A substance upon which the enzyme acts. Basics of Enzymes moving into the ECF.
• Heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR) (HF): ineffective pumping by the heart; results in venous congestion because blood does not move through the heart effectively. Presentation is with dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea on exertion and/or at rest, orthopnea Orthopnea Pulmonary Edema, and peripheral edema Peripheral edema Peripheral edema is the swelling of the lower extremities, namely, legs, feet, and ankles. Edema.
• Cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis: late stage of hepatic necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage and scarring Scarring Inflammation causing venous congestion in the portal veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology
• Lower-extremity deep vein thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus ( DVT DVT Deep vein thrombosis (DVT) usually occurs in the deep veins of the lower extremities. The affected veins include the femoral, popliteal, iliofemoral, and pelvic veins. Proximal DVT is more likely to cause a pulmonary embolism (PE) and is generally considered more serious. Deep Vein Thrombosis): occlusion of a deep vein by a thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus, most commonly occurring in the calves Calves Erythema Nodosum, causing venous congestion behind the occlusion

Hepatic Circulation

Arterial supply to the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy

• Abdominal aorta Abdominal Aorta The aorta from the diaphragm to the bifurcation into the right and left common iliac arteries. Posterior Abdominal Wall: Anatomy → celiac trunk → common hepatic artery Hepatic artery A branch of the celiac artery that distributes to the stomach, pancreas, duodenum, liver, gallbladder, and greater omentum. Liver: Anatomy 
• Carries oxygenated blood and nutrients to hepatocytes Hepatocytes The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. Liver: Anatomy
• Approximately 25% of the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy’s blood supply

Portal circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment

The portal vein Portal vein A short thick vein formed by union of the superior mesenteric vein and the splenic vein. Liver: Anatomy carries deoxygenated blood from the abdominal organs to the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy for 1st-pass metabolism of everything absorbed from the GI tract. 

• Pathway from the heart to the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy:
  • Aorta Aorta The main trunk of the systemic arteries. Mediastinum and Great Vessels: Anatomy → 
  • Celiac, superior and inferior mesenteric arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology (SMA, IMA) → 
  • Smaller named arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology → 
  • Capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries: Histology in GI villi → 
  • Smaller veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology → 
  • Portal vein Portal vein A short thick vein formed by union of the superior mesenteric vein and the splenic vein. Liver: Anatomy → portal venules Venules The minute vessels that collect blood from the capillary plexuses and join together to form veins. Veins: Histology within the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy
• Blood from the portal venules Venules The minute vessels that collect blood from the capillary plexuses and join together to form veins. Veins: Histology is filtered through hepatic sinusoids Sinusoids Liver: Anatomy lined by hepatocytes Hepatocytes The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. Liver: Anatomy:
  • Many substances absorbed via the GI tract are metabolized here by hepatocytes Hepatocytes The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. Liver: Anatomy.
  • Blood from the arterial supply also filters through hepatic sinusoids Sinusoids Liver: Anatomy.
• Blood flows into the central vein of a hepatic lobule → hepatic veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology → IVC IVC The venous trunk which receives blood from the lower extremities and from the pelvic and abdominal organs. Mediastinum and Great Vessels: Anatomy

Portosystemic anastomoses

Portosystemic anastomoses are points where 2 veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology connect with one another; in these cases, blood from 1 vein normally drains into the portal system, while blood from the other vein normally drains into systemic venous circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment (i.e., the IVC IVC The venous trunk which receives blood from the lower extremities and from the pelvic and abdominal organs. Mediastinum and Great Vessels: Anatomy).

• Ensures venous drainage of abdominal organs even if blockage occurs in portal system (e.g., cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis)
• Clinically important portosystemic anastomosis sites include:
  • Left gastric veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology and lower esophageal veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology 
  • Superior rectal veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology and the inferior and middle rectal veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology
  • Paraumbilical veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology and small epigastric veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology
  • Intraparenchymal hepatic branches of right division of portal vein Portal vein A short thick vein formed by union of the superior mesenteric vein and the splenic vein. Liver: Anatomy and retroperitoneal Retroperitoneal Peritoneum: Anatomy veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology 
  • Omental and colonic veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology with retroperitoneal Retroperitoneal Peritoneum: Anatomy veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology 
  • Ductus venosus Ductus venosus Development of the Heart and IVC IVC The venous trunk which receives blood from the lower extremities and from the pelvic and abdominal organs. Mediastinum and Great Vessels: Anatomy
• Clinical relevance: portal hypertension Portal hypertension Portal hypertension is increased pressure in the portal venous system. This increased pressure can lead to splanchnic vasodilation, collateral blood flow through portosystemic anastomoses, and increased hydrostatic pressure. There are a number of etiologies, including cirrhosis, right-sided congestive heart failure, schistosomiasis, portal vein thrombosis, hepatitis, and Budd-Chiari syndrome. Portal Hypertension
  • When pressures in the portal system rise, the portal vein Portal vein A short thick vein formed by union of the superior mesenteric vein and the splenic vein. Liver: Anatomy (and the veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology leading to it) become backed up.
  • Clinically may result in:
    • Esophageal varices (which may rupture, resulting in life-threatening hemorrhage)
    • Hemorrhoids Hemorrhoids Hemorrhoids are normal vascular cushions in the anal canal composed of dilated vascular tissue, smooth muscle, and connective tissue. They do not cause issues unless they are enlarged, inflamed, thrombosed, or prolapsed. Patients often present with rectal bleeding of bright red blood, or they may have pain, perianal pruritus, or a palpable mass. Hemorrhoids
    • Ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites
    • Hypersplenism Hypersplenism Condition characterized by splenomegaly, some reduction in the number of circulating blood cells in the presence of a normal or hyperactive bone marrow, and the potential for reversal by splenectomy. Splenomegaly (↑ pressure in the splenic vein)

Renal Circulation

Blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure

Blood flows to and through the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy via the following path:

• Aorta Aorta The main trunk of the systemic arteries. Mediastinum and Great Vessels: Anatomy → renal artery Renal artery A branch of the abdominal aorta which supplies the kidneys, adrenal glands and ureters. Glomerular Filtration → interlobar artery → arcuate artery → interlobular artery →
• Afferent arteriole Afferent arteriole Glomerular Filtration (brings arterial blood into the renal glomerulus) → 
• Glomerular capillaries Glomerular capillaries Kidneys: Anatomy
  • Blood is filtered in the glomerular capillaries Glomerular capillaries Kidneys: Anatomy.
  • The filtrate enters Bowman space → flows into the renal tubules and ultimately becomes urine →
• Efferent arteriole Efferent arteriole Glomerular Filtration (brings remaining arterial blood out of the glomerulus) →
• Peritubular and vasa recta Vasa recta Glomerular Filtration capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries: Histology
  • Peritubular capillaries Peritubular capillaries Glomerular Filtration: surround the proximal and distal tubules
  • Vasa recta Vasa recta Glomerular Filtration: surround the loops of Henle
  • These vessels are the beginning of venous circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment and are important in adjusting the contents of the urine →
• Interlobular vein → arcuate vein → interlobar vein → renal vein Renal vein Short thick veins which return blood from the kidneys to the vena cava. Glomerular Filtration → IVC IVC The venous trunk which receives blood from the lower extremities and from the pelvic and abdominal organs. Mediastinum and Great Vessels: Anatomy

Regulation of glomerular filtration Glomerular filtration The kidneys are primarily in charge of the maintenance of water and solute homeostasis through the processes of filtration, reabsorption, secretion, and excretion. Glomerular filtration is the process of converting the systemic blood supply into a filtrate, which will ultimately become the urine. Glomerular Filtration

The kidney has multiple levels of regulatory mechanisms that affect renal blood flow Renal blood flow The amount of the renal blood flow that is going to the functional renal tissue, i.e., parts of the kidney that are involved in production of urine. Glomerular Filtration (RBF) and the glomerular filtration rate Glomerular filtration rate The volume of water filtered out of plasma through glomerular capillary walls into Bowman’s capsules per unit of time. It is considered to be equivalent to inulin clearance. Kidney Function Tests ( GFR GFR The volume of water filtered out of plasma through glomerular capillary walls into Bowman’s capsules per unit of time. It is considered to be equivalent to inulin clearance. Kidney Function Tests): 

Relative constriction and dilation of the afferent Afferent Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology and efferent Efferent Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology arterioles Arterioles The smallest divisions of the arteries located between the muscular arteries and the capillaries. Arteries: Histology:

• Afferent arteriole Afferent arteriole Glomerular Filtration:
  • Constriction: ↓ RBF → ↓ hydrostatic pressure Hydrostatic pressure The pressure due to the weight of fluid. Edema in the glomerular capillaries Glomerular capillaries Kidneys: Anatomy → ↓ GFR GFR The volume of water filtered out of plasma through glomerular capillary walls into Bowman’s capsules per unit of time. It is considered to be equivalent to inulin clearance. Kidney Function Tests 
  • Dilation: ↑ RBF → ↑ hydrostatic pressure Hydrostatic pressure The pressure due to the weight of fluid. Edema in the glomerular capillaries Glomerular capillaries Kidneys: Anatomy → ↑ GFR GFR The volume of water filtered out of plasma through glomerular capillary walls into Bowman’s capsules per unit of time. It is considered to be equivalent to inulin clearance. Kidney Function Tests 
• Efferent arteriole Efferent arteriole Glomerular Filtration:
  • Constriction: ↑ hydrostatic pressure Hydrostatic pressure The pressure due to the weight of fluid. Edema in glomerular capillaries Glomerular capillaries Kidneys: Anatomy → ↑ GFR GFR The volume of water filtered out of plasma through glomerular capillary walls into Bowman’s capsules per unit of time. It is considered to be equivalent to inulin clearance. Kidney Function Tests but ↓ RBF
  • Dilation: ↓ hydrostatic pressure Hydrostatic pressure The pressure due to the weight of fluid. Edema in glomerular capillaries Glomerular capillaries Kidneys: Anatomy → ↓ GFR GFR The volume of water filtered out of plasma through glomerular capillary walls into Bowman’s capsules per unit of time. It is considered to be equivalent to inulin clearance. Kidney Function Tests but ↑ RBF

Autoregulation of the renal blood flow Renal blood flow The amount of the renal blood flow that is going to the functional renal tissue, i.e., parts of the kidney that are involved in production of urine. Glomerular Filtration (RBF):

• Myogenic response Myogenic response Glomerular Filtration: ↑ systemic blood pressure stretches afferent Afferent Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology arterioles Arterioles The smallest divisions of the arteries located between the muscular arteries and the capillaries. Arteries: Histology → activates inward-directed ion channels Channels The Cell: Cell Membrane → depolarization Depolarization Membrane Potential → arteriole contraction
  • ↑ Systemic BP → afferent arteriole Afferent arteriole Glomerular Filtration vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure → ↓ RBF
  • ↓ Systemic BP → afferent arteriole Afferent arteriole Glomerular Filtration vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs → ↑ RBF
• Maintains relatively constant RBF within a range of normal mean arterial blood pressures (the autoregulatory range)
• Stable RBF allows the other regulatory mechanisms (rather than systemic BP) to regulate the GFR GFR The volume of water filtered out of plasma through glomerular capillary walls into Bowman’s capsules per unit of time. It is considered to be equivalent to inulin clearance. Kidney Function Tests.

Tubuloglomerular feedback Tubuloglomerular feedback Glomerular Filtration:

Macula Macula An oval area in the retina, 3 to 5 mm in diameter, usually located temporal to the posterior pole of the eye and slightly below the level of the optic disk. It is characterized by the presence of a yellow pigment diffusely permeating the inner layers, contains the fovea centralis in its center, and provides the best phototropic visual acuity. It is devoid of retinal blood vessels, except in its periphery, and receives nourishment from the choriocapillaris of the choroid. Eye: Anatomy densa (MD) cells within the tubules can sense tubular flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure and adjust secretion Secretion Coagulation Studies of substances that affect GFR GFR The volume of water filtered out of plasma through glomerular capillary walls into Bowman’s capsules per unit of time. It is considered to be equivalent to inulin clearance. Kidney Function Tests:

• Macula Macula An oval area in the retina, 3 to 5 mm in diameter, usually located temporal to the posterior pole of the eye and slightly below the level of the optic disk. It is characterized by the presence of a yellow pigment diffusely permeating the inner layers, contains the fovea centralis in its center, and provides the best phototropic visual acuity. It is devoid of retinal blood vessels, except in its periphery, and receives nourishment from the choriocapillaris of the choroid. Eye: Anatomy densa cells (located in distal tubules):
  • Sense the relative flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure of NaCl, which correlates directly with GFR GFR The volume of water filtered out of plasma through glomerular capillary walls into Bowman’s capsules per unit of time. It is considered to be equivalent to inulin clearance. Kidney Function Tests
  • ↑ NaCl flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure = ↑ GFR GFR The volume of water filtered out of plasma through glomerular capillary walls into Bowman’s capsules per unit of time. It is considered to be equivalent to inulin clearance. Kidney Function Tests
  • MD cells can:
    • Secrete adenosine Adenosine A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. Class 5 Antiarrhythmic Drugs
    • Independently stimulate juxtaglomerular cells to secrete renin Renin A highly specific (leu-leu) endopeptidase that generates angiotensin I from its precursor angiotensinogen, leading to a cascade of reactions which elevate blood pressure and increase sodium retention by the kidney in the renin-angiotensin system. Renal Sodium and Water Regulation
• Adenosine Adenosine A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. Class 5 Antiarrhythmic Drugs: ↓ GFR GFR The volume of water filtered out of plasma through glomerular capillary walls into Bowman’s capsules per unit of time. It is considered to be equivalent to inulin clearance. Kidney Function Tests by constricting afferent Afferent Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology arterioles Arterioles The smallest divisions of the arteries located between the muscular arteries and the capillaries. Arteries: Histology 
• Renin Renin A highly specific (leu-leu) endopeptidase that generates angiotensin I from its precursor angiotensinogen, leading to a cascade of reactions which elevate blood pressure and increase sodium retention by the kidney in the renin-angiotensin system. Renal Sodium and Water Regulation: ↑ GFR GFR The volume of water filtered out of plasma through glomerular capillary walls into Bowman’s capsules per unit of time. It is considered to be equivalent to inulin clearance. Kidney Function Tests by activating the RAAS RAAS A blood pressure regulating system of interacting components that include renin; angiotensinogen; angiotensin converting enzyme; angiotensin i; angiotensin ii; and angiotensinase. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. Angiotensin-converting enzyme, contained in the lung, acts on angiotensin I in the plasma converting it to angiotensin II, an extremely powerful vasoconstrictor. Angiotensin II causes contraction of the arteriolar and renal vascular smooth muscle, leading to retention of salt and water in the kidney and increased arterial blood pressure. In addition, angiotensin II stimulates the release of aldosterone from the adrenal cortex, which in turn also increases salt and water retention in the kidney. Angiotensin-converting enzyme also breaks down bradykinin, a powerful vasodilator and component of the kallikrein-kinin system. Adrenal Hormones
  • ↑ Renin Renin A highly specific (leu-leu) endopeptidase that generates angiotensin I from its precursor angiotensinogen, leading to a cascade of reactions which elevate blood pressure and increase sodium retention by the kidney in the renin-angiotensin system. Renal Sodium and Water Regulation → ↑ angiotensin I → ↑ angiotensin II Angiotensin II An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the c-terminal by angiotensin converting enzyme. The amino acid in position 5 varies in different species. To block vasoconstriction and hypertension effect of angiotensin II, patients are often treated with ace inhibitors or with angiotensin II type 1 receptor blockers. Renal Sodium and Water Regulation → ↑ aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia
  • RAAS RAAS A blood pressure regulating system of interacting components that include renin; angiotensinogen; angiotensin converting enzyme; angiotensin i; angiotensin ii; and angiotensinase. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. Angiotensin-converting enzyme, contained in the lung, acts on angiotensin I in the plasma converting it to angiotensin II, an extremely powerful vasoconstrictor. Angiotensin II causes contraction of the arteriolar and renal vascular smooth muscle, leading to retention of salt and water in the kidney and increased arterial blood pressure. In addition, angiotensin II stimulates the release of aldosterone from the adrenal cortex, which in turn also increases salt and water retention in the kidney. Angiotensin-converting enzyme also breaks down bradykinin, a powerful vasodilator and component of the kallikrein-kinin system. Adrenal Hormones activation results in:
    • Systemic vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure → ↑ blood pressure to maintain RBF
    • More vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure of the efferent arteriole Efferent arteriole Glomerular Filtration → ↑ GFR GFR The volume of water filtered out of plasma through glomerular capillary walls into Bowman’s capsules per unit of time. It is considered to be equivalent to inulin clearance. Kidney Function Tests (but ↓ in RBF)
    • ↑ Na and water reabsorption → ↑ in systemic blood pressure and RBF
• Examples of tubuloglomerular feedback Tubuloglomerular feedback Glomerular Filtration:
  • ↑ Tubular NaCl flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure → MD senses ↑ flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure → releases adenosine Adenosine A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. Class 5 Antiarrhythmic Drugs (and inhibits renin Renin A highly specific (leu-leu) endopeptidase that generates angiotensin I from its precursor angiotensinogen, leading to a cascade of reactions which elevate blood pressure and increase sodium retention by the kidney in the renin-angiotensin system. Renal Sodium and Water Regulation) → GFR GFR The volume of water filtered out of plasma through glomerular capillary walls into Bowman’s capsules per unit of time. It is considered to be equivalent to inulin clearance. Kidney Function Tests ↓ (normalizes)
  • ↓ Tubular NaCl flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure → MD senses ↓ flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure → stimulates the release of renin Renin A highly specific (leu-leu) endopeptidase that generates angiotensin I from its precursor angiotensinogen, leading to a cascade of reactions which elevate blood pressure and increase sodium retention by the kidney in the renin-angiotensin system. Renal Sodium and Water Regulation (and inhibits adenosine Adenosine A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. Class 5 Antiarrhythmic Drugs) → GFR GFR The volume of water filtered out of plasma through glomerular capillary walls into Bowman’s capsules per unit of time. It is considered to be equivalent to inulin clearance. Kidney Function Tests ↑ (normalizes)

Fine-tuning mechanisms: 

• Paracrine mechanisms Paracrine mechanisms Cellular signaling in which a factor secreted by a cell affects other cells in the local environment. This term is often used to denote the action of intercellular signaling peptides and proteins on surrounding cells. Glomerular Filtration: local release of vasoactive substances
  • Vasoconstrictors (e.g., endothelins Endothelins 21-amino-acid peptides produced by vascular endothelial cells and functioning as potent vasoconstrictors. The endothelin family consists of three members, endothelin-1; endothelin-2; and endothelin-3. All three peptides contain 21 amino acids, but vary in amino acid composition. The three peptides produce vasoconstrictor and pressor responses in various parts of the body. However, the quantitative profiles of the pharmacological activities are considerably different among the three isopeptides. Hemostasis): ↓ RBF
  • Vasodilators Vasodilators Drugs used to cause dilation of the blood vessels. Thromboangiitis Obliterans (Buerger’s Disease) (e.g., nitric oxide Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from arginine by nitric oxide synthase. Nitric oxide is one of the endothelium-dependent relaxing factors released by the vascular endothelium and mediates vasodilation. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic gmp. Pulmonary Hypertension Drugs, prostaglandins Prostaglandins A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. Eicosanoids): ↑ RBF
• Endocrine mechanisms Endocrine mechanisms Glomerular Filtration:
  • RAAS RAAS A blood pressure regulating system of interacting components that include renin; angiotensinogen; angiotensin converting enzyme; angiotensin i; angiotensin ii; and angiotensinase. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. Angiotensin-converting enzyme, contained in the lung, acts on angiotensin I in the plasma converting it to angiotensin II, an extremely powerful vasoconstrictor. Angiotensin II causes contraction of the arteriolar and renal vascular smooth muscle, leading to retention of salt and water in the kidney and increased arterial blood pressure. In addition, angiotensin II stimulates the release of aldosterone from the adrenal cortex, which in turn also increases salt and water retention in the kidney. Angiotensin-converting enzyme also breaks down bradykinin, a powerful vasodilator and component of the kallikrein-kinin system. Adrenal Hormones
  • Natriuretic peptides Natriuretic peptides Peptides that regulate the water-electrolyte balance in the body, also known as natriuretic peptide hormones. Several have been sequenced (atrial natriuretic factor; brain natriuretic peptide; c-type natriuretic peptide). Arterial Pressure Regulation
• Neural mechanisms Neural mechanisms Glomerular Filtration: sympathetic mediated vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure → ↓ RBF

Cerebral Circulation

Cerebral circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment is unique because its vessels are protected by a specialized structure called the blood–brain barrier Blood–Brain Barrier Meningitis in Children, and it has the ability to regulate its own blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure.

Blood–brain barrier Blood–Brain Barrier Meningitis in Children

• Prevents many harmful substances Harmful substances Elements, compounds, mixtures, or solutions that are considered severely harmful to human health and the environment. They include substances that are toxic, corrosive, flammable, or explosive. Esophagitis (e.g., toxins, bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology) from affecting brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification parenchyma
• Allows passage of ions and nutrients
• Structurally created by:
  • Foot-like processes of astrocytes Astrocytes A class of large neuroglial (macroglial) cells in the central nervous system – the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from ‘star’ cells) are irregularly shaped with many long processes, including those with ‘end feet’ which form the glial (limiting) membrane and directly and indirectly contribute to the blood-brain barrier. They regulate the extracellular ionic and chemical environment, and ‘reactive astrocytes’ (along with microglia) respond to injury. Nervous System: Histology wrapping around cerebral capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries: Histology, limiting substances that can escape Escape With constant immune mechanisms holding unstable tumor cells in equilibrium, tumor-cell variants may emerge. These cancer cells may express fewer antigens on their surfaces or lose their MHC class I expression.Variants may also protect themselves from T-cell attack via expression of IC molecules on their surfaces, like normal cells.Creation of an immunosuppressive state in the microenvironment is another way to grow without immunologic interference. Cancer Immunotherapy the vasculature 
  • No fenestrations in capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries: Histology
  • Tight junctions Tight junctions Cell-cell junctions that seal adjacent epithelial cells together, preventing the passage of most dissolved molecules from one side of the epithelial sheet to the other. The Cell: Cell Junctions prevent paracellular Paracellular Renal Potassium Regulation diffusion Diffusion The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space. Diffusion, especially facilitated diffusion, is a major mechanism of biological transport. Peritoneal Dialysis and Hemodialysis

Autoregulatory ability

The brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification can regulate its own cerebral blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure (CBF) in response to changes in blood pressure, CO₂ levels, and activity levels of different brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification regions.

• Myogenic autoregulatory ability in response to changes in mean arterial pressures (MAPs) (similar to the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy):
  • ↑ Systemic MAPs : cerebral arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology vasoconstrict, limiting flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure
  • ↓ Systemic MAPs: cerebral arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology vasodilate, maintaining perfusion
  • Autoregulatory ability functions between MAPs of 60 and 150 mm Hg
    • < 60 mm Hg: CBF ↓ because there simply is not enough pressure to perfuse the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification
    • > 150 mm Hg: CBF ↑ because the pressure overwhelms the autoregulatory system
• CO₂-induced vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs:
  • ↓ Perfusion → CO₂ accumulates → ↓ pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance → triggers vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs → ↑ flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure
  • Hypocapnia (i.e., ↓ CO₂) → ↑ pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance → vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure → ↓ flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure
  • Clinical relevance: hyperventilation Hyperventilation A pulmonary ventilation rate faster than is metabolically necessary for the exchange of gases. It is the result of an increased frequency of breathing, an increased tidal volume, or a combination of both. It causes an excess intake of oxygen and the blowing off of carbon dioxide. Respiratory Alkalosis
    • Exhaling CO₂ faster than the body produces it
    • Results in hypocapnia → cerebral vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure → ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage, dizziness Dizziness An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. Lateral Medullary Syndrome (Wallenberg Syndrome), and potentially syncope Syncope Syncope is a short-term loss of consciousness and loss of postural stability followed by spontaneous return of consciousness to the previous neurologic baseline without the need for resuscitation. The condition is caused by transient interruption of cerebral blood flow that may be benign or related to a underlying life-threatening condition. Syncope
• Redistribution of blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure throughout the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification according to tasks being performed
  • For example, motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology versus sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology versus cognitive functions
  • Occurs in a matter of seconds
  • Due to effects of local metabolites

Coronary and Skeletal Muscle Circulation

Coronary circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment

The heart does not receive significant O₂ and nutrients from the blood flowing through it. Coronary circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment describes the flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure of blood through the vessels supplying the heart muscle itself.

• There are 2 primary coronary arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology:
  • The left coronary artery Left coronary artery Heart: Anatomy (LCA) divides into:
    • Anterior interventricular artery (i.e., the left anterior descending (LAD) artery)
    • Left circumflex artery
  • The right coronary artery Right coronary artery Heart: Anatomy (RCA) divides into:
    • Posterior interventricular artery (i.e., posterior descending artery ( PDA PDA The ductus arteriosus (DA) allows blood to bypass pulmonary circulation. After birth, the DA remains open for up to 72 hours and then constricts and involutes, becoming the ligamentum arteriosum. Failure of this process to occur results in patent ductus arteriosus (PDA), a condition that causes up to 10% of congenital heart defects. Patent Ductus Arteriosus (PDA)))
    • Right marginal artery
  • Both the LCA and the RCA originate from the aorta Aorta The main trunk of the systemic arteries. Mediastinum and Great Vessels: Anatomy, just above the aortic valve Aortic valve The valve between the left ventricle and the ascending aorta which prevents backflow into the left ventricle. Heart: Anatomy. 
  • Clinical relevance: occlusion of these vessels (typically via a thrombus), results in rapid ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage and potential necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage of surrounding myocardial tissue; this is known as a myocardial infarction Myocardial infarction MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction ( MI MI MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction; i.e., heart attack Heart attack Mi is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction)
• The heart is primarily irrigated during diastole Diastole Post-systolic relaxation of the heart, especially the heart ventricles. Cardiac Cycle (relaxation of the heart muscle):
  • During systole Systole Period of contraction of the heart, especially of the heart ventricles. Cardiac Cycle, the small vessels perforating/supplying the cardiac muscle Cardiac muscle The muscle tissue of the heart. It is composed of striated, involuntary muscle cells connected to form the contractile pump to generate blood flow. Muscle Tissue: Histology are compressed.
  • The faster the heart beats = shorter diastole Diastole Post-systolic relaxation of the heart, especially the heart ventricles. Cardiac Cycle = less time heart has for irrigation
• Autoregulation: like the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification and kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy, the heart has the ability to vasodilate and/or vasoconstrict coronary vessels across a range of MAPs to maintain a steady flow rate Flow rate maximum flow the ventilator will deliver a set tidal volume in liters per minute Invasive Mechanical Ventilation.

Skeletal muscle circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment

Actively contracting muscles increase their own blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure.

• Sympathetic activation via the sympathetic nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification (SNS):
  • Causes vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure of arterioles Arterioles The smallest divisions of the arteries located between the muscular arteries and the capillaries. Arteries: Histology (and thus limits blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure) in skeletal muscle 
  • Responsible for maintaining arterial blood pressure under resting circumstances
  • Via:
    • Sympathetic nerves
    • Circulating catecholamines Catecholamines A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine. Adrenal Hormones ( epinephrine Epinephrine The active sympathomimetic hormone from the adrenal medulla. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. Sympathomimetic Drugs and norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS) released from the adrenal medulla Adrenal Medulla The inner portion of the adrenal gland. Derived from ectoderm, adrenal medulla consists mainly of chromaffin cells that produces and stores a number of neurotransmitters, mainly adrenaline (epinephrine) and norepinephrine. The activity of the adrenal medulla is regulated by the sympathetic nervous system. Adrenal Glands: Anatomy
• Production of local factors causes vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs of arterioles Arterioles The smallest divisions of the arteries located between the muscular arteries and the capillaries. Arteries: Histology and precapillary sphincters Precapillary Sphincters Capillaries: Histology:
  • The precapillary sphincters Precapillary Sphincters Capillaries: Histology lack innervation → are regulated primarily by production of these local factors
  • Factors include:
    • Lactic acid
    • CO₂
    • Adenosine Adenosine A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. Class 5 Antiarrhythmic Drugs
• Functional sympatholysis Functional sympatholysis Cardiovascular Response to Exercise: local factors causing vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs overcome any SNS stimulation, resulting in vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs during activity.
• Blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure to skeletal muscles Skeletal muscles A subtype of striated muscle, attached by tendons to the skeleton. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles. Muscle Tissue: Histology can increase > 20-fold during strenuous exercise Strenuous exercise Physical activity which is usually regular and done with the intention of improving or maintaining physical fitness or health. Contrast with physical exertion which is concerned largely with the physiologic and metabolic response to energy expenditure. Cardiovascular Response to Exercise.
• Like cardiac muscle Cardiac muscle The muscle tissue of the heart. It is composed of striated, involuntary muscle cells connected to form the contractile pump to generate blood flow. Muscle Tissue: Histology, flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure is restricted during muscle contraction owing to compression Compression Blunt Chest Trauma of smaller vessels.
• Isometric contractions Isometric contractions Muscular contractions characterized by increase in tension without change in length. Cardiovascular Response to Exercise cause fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia more quickly than intermittent isotonic Isotonic Solutions having the same osmotic pressure as blood serum, or another solution with which they are compared. Renal Sodium and Water Regulation contractions.
  • Isometric contractions Isometric contractions Muscular contractions characterized by increase in tension without change in length. Cardiovascular Response to Exercise: sustained contractions with no change in muscle length
  • Isotonic Isotonic Solutions having the same osmotic pressure as blood serum, or another solution with which they are compared. Renal Sodium and Water Regulation contractions: change in muscle length producing limb motion

Cutaneous Circulation

Regulating vascular flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure to the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions is critical to thermoregulation Thermoregulation Body temperature can be divided into external temperature, which involves the skin, and core temperature, which involves the CNS and viscera. While external temperature can be variable, the core temperature is maintained within a narrow range of 36.5-37.5ºC (97.7-99.5ºF). Body Temperature Regulation because heat Heat Inflammation is dissipated as blood flows near the surface of the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions.

Nonglabrous skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions

Nonglabrous skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions is thin skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions with hair on it.

• Under stable temperatures: flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure is low and stable.
• In response to systemic cold (i.e., whole-body cold thermal stress):
  • Sympathetic activation → vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure → prevents excess heat Heat Inflammation loss from blood moving too close to the surface 
  • Via epinephrine Epinephrine The active sympathomimetic hormone from the adrenal medulla. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. Sympathomimetic Drugs on α₁– and α₂-adrenergic receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors
• In response to local cold:
  • Vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure is mediated through local translocation of α_2c-adrenergic receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors to the cell surface.
  • Not mediated via systemic sympathetic activation
• In response to systemic heat Heat Inflammation (i.e., whole-body hot thermal stress):
  • Release of vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure
  • Activation of vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs → allows more blood near the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions surface to dissipate the heat Heat Inflammation
  • Via acetylcholine Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS and an unknown molecule (thought to be related to NO, which causes smooth muscle dilation)
• In response to local heat Heat Inflammation:
  • Axon reflex: triggers a rapid increase in vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs
  • NO: sustains maximal vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs

Glabrous skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions

Glabrous skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions is thicker skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions without hair on it (e.g., palms, soles, ear lobes):

• Tonic sympathetic activation → almost always vasoconstricted, but can be increased
• Mediated via:
  • Norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS
  • Neuropeptide Y 
• Has AV anastomoses:
  • Shunts that bypass the capillary beds Capillary beds Groups of 10–100 individual capillary vessels supplied by a single metarteriole. Capillaries: Histology closer to the surface of the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions
  • Allows for greater amounts of blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure without loss of heat Heat Inflammation
• Glabrous skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions has no active vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs: flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure increases by releasing vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure.
• In response to local heat Heat Inflammation or cold: opening and closing the AV anastomoses allows for alterations in blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure.

Wheal Wheal Urticaria (Hives) and flare (the triple response)

• A localized skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions response occurring in response to an allergen (e.g., allergy Allergy An abnormal adaptive immune response that may or may not involve antigen-specific IgE Type I Hypersensitivity Reaction testing and mosquito bites)
• Wheal Wheal Urticaria (Hives) ( swelling Swelling Inflammation):
  • Caused by fluid leaking from the blood vessels following mast-cell activation
  • Mast-cell activation → histamine release → histamine increases capillary permeability → more fluid leaks from the blood into the interstitial space
• Flare (appears red): caused by local vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs and increased blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure