Systemic and Special Circulations

Circulation is the movement of blood throughout the body through one continuous circuit of blood vessels. Different organs have unique functions and, therefore, have different requirements, circulatory patterns, and regulatory mechanisms. Several of the most vital organs (including the brain, heart, 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) have autoregulatory properties, meaning that they are able to maintain a relatively constant blood flow despite fluctuations in mean arterial pressure (MAP). In other cases, locally produced factors (such as adenosine, CO2, or NO) can produce local vasoconstriction or vasodilation, regulating blood flow under specific physiologic conditions.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Overview of Systemic Circulation and Capillary Exchange

Anatomy review of systemic and pulmonary circulation

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 in one direction, sequentially through the following structures: 

  • Deoxygenated blood enters the heart via the superior vena cava (SVC) and the inferior vena cava (IVC) → 
  • Right atrium (RA) → tricuspid valve → right ventricle (RV) → pulmonary valve → 
  • Pulmonary trunk → 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 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:
    • 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 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 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 > hydrostatic pressure 
      • strongly favors 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 stenosis) 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.
  • Pulmonary 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 → left atrium (LA) → mitral valve → left ventricle (LV) → aortic valve → 
  • Aorta → 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 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 (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 → SVC/IVC → back to the heart
Circulation of blood through the body

Circulation of blood through the body:
Deoxygenated blood enters the right side of the heart and passes through the pulmonary trunk to 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, where it is oxygenated. The blood then returns to the left side of the heart via the pulmonary 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, where it is pumped into the aorta and distributed throughout the body. The blood travels through systemic 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, where it is deoxygenated again, and travels back to the heart via the superior and inferior vena cava.
LA: left atrium
LV: left ventricle
RA: right atrium
RV: right ventricle

Image by Lecturio.

Distribution of blood flow

  • At rest, the majority of cardiac output 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: approximately 25%
    • Kidneys: approximately 20%
    • Skeletal muscle: approximately 20%
    • Brain: approximately 15%
  • Vascular beds receive 5%–10% of blood flow:
    • 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. Structure and Function of the Skin: approximately 7%
    • Intestines: approximately 5%
    • Heart: approximately 5%
  • Other vascular beds: approximately 3%
  • Vascular beds can increase their blood flow through vasodilation (some organs much more so than others)
    • Skeletal muscle: can substantially ↑ blood flow through vasodilation
    • Heart: has the lowest ability to ↑ blood flow 
    • Brain: although it has the ability to increase flow, of all the organs, keeps flow the most constant

Blood flow 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

  • Blood enters the capillary beds through the arterioles → metarterioles → 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
  • Blood drains into the thoroughfare channel → empties into venules
  • Metarterioles contain smooth muscle precapillary sphincters at the entrance to each individual capillary:
    • Regulates the amount of blood flow 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 and flows straight through the thoroughfare channel.
  • Arteriovenous anastomoses (AV shunts): vessels that bypass the capillary beds and directly connect 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 and 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
    • AV shunts are present when precapillary sphincters are closed.
    • Numerous in the dermis: help regulate body heat
Capillary bed

Capillary bed demonstrating arteriole, metarteriole, precapillary sphincters, thoroughfare channel, and venule

Image: “Capillary bed” by OpenStax College. License: CC BY 3.0

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

Functions:

  • Gas exchange: 
    • O2 leaves the RBCs.
    • CO2 enters the RBCs.
  • Nutrient delivery
  • Blood picks up cellular and interstitial waste.

Starling forces 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:

  • Relatively higher hydrostatic pressure in the arterioles pushes fluid, nutrients, and other cellular material into the surrounding extracellular fluid (ECF).
  • Plasma proteins generally cannot pass through the capillary walls → plasma oncotic pressure ↑ toward the venous end of the capillary
  • Relatively higher oncotic pressure in the venules allow waste to be absorbed into the vessels.

Clinical relevance of increased hydrostatic pressure 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:

  • Any condition that prevents blood flow from moving forward on the venous side can lead to an increase in hydrostatic pressure 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, which will result in more fluid and substrate moving into the ECF.
  • Congestive heart failure Congestive heart failure Congestive heart failure refers to the inability of the heart to supply the body with normal cardiac output to meet metabolic needs. Echocardiography can confirm the diagnosis and give information about the ejection fraction. Congestive Heart Failure ( CHF CHF Congestive heart failure refers to the inability of the heart to supply the body with normal cardiac output to meet metabolic needs. Echocardiography can confirm the diagnosis and give information about the ejection fraction. Congestive Heart Failure): 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, and peripheral edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). 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 and scarring 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
  • Lower-extremity deep vein thrombosis Deep vein thrombosis 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 ( 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, most commonly occurring in the calves, causing venous congestion behind the occlusion
Starling forces within a capillary

Starling forces:
Starling forces within a capillary determine the flow of molecules into and out of the vessel.

Image: “Net filtration” by Phil Schatz. License: CC BY 4.0

Hepatic Circulation

Arterial supply to the liver

  • Abdominal aorta → celiac trunk → common hepatic artery 
  • Carries oxygenated blood and nutrients to hepatocytes
  • Approximately 25% of the liver’s blood supply

Portal circulation

The portal vein carries deoxygenated blood from the abdominal organs to the liver for 1st-pass metabolism of everything absorbed from the GI tract. 

  • Pathway from the heart to the liver:
    • Aorta → 
    • 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 ( SMA SMA Spinal muscular atrophy (SMA) is a spectrum of autosomal recessive syndromes characterized by progressive proximal muscle weakness and atrophy, possibly due to degeneration of the anterior horn cells in the spinal cord and motor nuclei in the lower brainstem. Spinal Muscular Atrophy (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 → 
    • Capillaries 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 → 
    • Portal vein → portal venules within the liver
  • Blood from the portal venules is filtered through hepatic sinusoids lined by hepatocytes: 
    • Many substances absorbed via the GI tract are metabolized here by hepatocytes.
    • Blood from the arterial supply also filters through hepatic sinusoids.
  • 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 → IVC
Anatomy of a hepatic lobule

Anatomy of a hepatic lobule:
Blood to be filtered enters through the portal venules and flows through the sinusoids and into the central vein. From there, the blood flows out through the 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 and into the inferior vena cava.

Image: “Microscopic Anatomy 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” by OpenStax College. License: CC BY 4.0

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 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 (i.e., the IVC).

  • Ensures venous drainage of abdominal organs even if blockage occurs in portal system (e.g., 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 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 
    • 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 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
    • 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 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
    • Intraparenchymal hepatic branches of right division of portal vein and retroperitoneal 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 
    • 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 with retroperitoneal 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 
    • Ductus venosus and IVC
  • 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 (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 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
      • Hypersplenism (↑ pressure in the splenic vein)
Esophageal varices, splenomegaly, and rectal varices in portal hypertension

Esophageal varices, splenomegaly Splenomegaly Splenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly, and rectal varices resulting from backup of blood flow due to elevated pressures within the portal vein

Image by Lecturio.

Renal Circulation

Blood flow

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 via the following path:

  • Aorta → renal artery → interlobar artery → arcuate artery → interlobular artery
  • Afferent arteriole (brings arterial blood into the renal glomerulus) → 
  • Glomerular 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 
    • Blood is filtered in the glomerular 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.
    • The filtrate enters Bowman space → flows into the renal tubules and ultimately becomes urine →
  • Efferent arteriole (brings remaining arterial blood out of the glomerulus) →
  • Peritubular and vasa recta 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 
    • Peritubular 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: surround the proximal and distal tubules
    • Vasa recta: surround the loops of Henle
    • These vessels are the beginning of venous circulation and are important in adjusting the contents of the urine →
  • Interlobular vein → arcuate vein → interlobar vein → renal vein → IVC
Renal circulation

Renal circulation

Image by Lecturio.

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 (RBF) and the 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 rate (GFR): 

Relative constriction and dilation of the afferent and efferent arterioles:

  • Afferent arteriole:
    • Constriction: ↓ RBF → ↓ hydrostatic pressure in the glomerular 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 → ↓ GFR 
    • Dilation: ↑ RBF → ↑ hydrostatic pressure in the glomerular 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 → ↑ GFR 
  • Efferent arteriole: 
    • Constriction: ↑ hydrostatic pressure in glomerular 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 → ↑ GFR but ↓ RBF
    • Dilation: ↓ hydrostatic pressure in glomerular 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 → ↓ GFR but ↑ RBF

Autoregulation of the renal blood flow (RBF):

  • Myogenic response: ↑ systemic blood pressure stretches afferent arterioles → activates inward-directed ion channels → depolarization → arteriole contraction
    • ↑ Systemic BP → afferent arteriole vasoconstriction → ↓ RBF
    • ↓ Systemic BP → afferent arteriole vasodilation → ↑ 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.
Impact of mean arterial blood pressure on the flow rate of renal blood flow (rbf) and glomerular filtration rate (gfr)

Impact of mean arterial blood pressure on the flow rate of renal blood flow (RBF) and 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 rate (GFR):
Notice that within the autoregulatory range, GFR and RBF remain relatively constant.

Image by Lecturio.

Tubuloglomerular feedback:

Macula densa (MD) cells within the tubules can sense tubular flow and adjust secretion of substances that affect GFR:

  • Macula densa cells (located in distal tubules):
    • Sense the relative flow of NaCl, which correlates directly with GFR
    • ↑ NaCl flow = ↑ GFR
    • MD cells can:
      • Secrete adenosine
      • Independently stimulate juxtaglomerular cells to secrete renin
  • Adenosine: ↓ GFR by constricting afferent arterioles 
  • Renin: ↑ GFR by activating the RAAS
    • ↑ Renin → ↑ angiotensin I → ↑ angiotensin II → ↑ aldosterone
    • RAAS activation results in:
      • Systemic vasoconstriction → ↑ blood pressure to maintain RBF
      • More vasoconstriction of the efferent arteriole → ↑ GFR (but ↓ in RBF)
      • ↑ Na and water reabsorption → ↑ in systemic blood pressure and RBF
  • Examples of tubuloglomerular feedback:
    • ↑ Tubular NaCl flow → MD senses ↑ flow → releases adenosine (and inhibits renin) → GFR ↓ (normalizes)
    • ↓ Tubular NaCl flow → MD senses ↓ flow → stimulates the release of renin (and inhibits adenosine) → GFR ↑ (normalizes)

Fine-tuning mechanisms: 

  • Paracrine mechanisms: local release of vasoactive substances
    • Vasoconstrictors (e.g., endothelins): ↓ RBF
    • Vasodilators (e.g., nitric oxide, prostaglandins): ↑ RBF
  • Endocrine mechanisms: 
    • RAAS
    • Natriuretic peptides
  • Neural mechanisms: sympathetic mediated vasoconstriction → ↓ RBF

Cerebral Circulation

Cerebral circulation is unique because its vessels are protected by a specialized structure called the blood–brain barrier, and it has the ability to regulate its own blood flow.

Blood–brain barrier

  • Prevents many harmful substances (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: Overview) from affecting brain parenchyma
  • Allows passage of ions and nutrients
  • Structurally created by:
    • Foot-like processes of astrocytes 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, limiting substances that can escape 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
    • Tight junctions prevent paracellular diffusion
The blood–brain barrier

The blood–brain barrier

Image by Lecturio.

Autoregulatory ability

The brain can regulate its own cerebral blood flow (CBF) in response to changes in blood pressure, CO2 levels, and activity levels of different brain 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):
    • ↑ 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 vasoconstrict, limiting flow
    • ↓ 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 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
      • > 150 mm Hg: CBF ↑ because the pressure overwhelms the autoregulatory system
  • CO2-induced vasodilation:
    • ↓ Perfusion → CO2 accumulates → ↓ pH → triggers vasodilation → ↑ flow
    • Hypocapnia (i.e., ↓ CO2) → ↑ pH → vasoconstriction → ↓ flow
    • Clinical relevance: hyperventilation
      • Exhaling CO2 faster than the body produces it
      • Results in hypocapnia → cerebral vasoconstriction → ischemia, dizziness, 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 throughout the brain according to tasks being performed 
    • For example, motor versus sensory versus cognitive functions
    • Occurs in a matter of seconds
    • Due to effects of local metabolites
Blood flow redistribution in the brain according to different tasks

Blood flow redistribution in the brain according to the task being performed:
Redistribution depends heavily on the metabolic activity of the different portions of the cerebral tissue.

Image by Lecturio.

Coronary and Skeletal Muscle Circulation

Coronary circulation

The heart does not receive significant O2 and nutrients from the blood flowing through it. Coronary circulation describes the flow 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:
    • The left coronary artery (LCA) divides into:
      • Anterior interventricular artery (i.e., the left anterior descending (LAD) artery)
      • Left circumflex artery
    • The right coronary artery (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, just above the aortic valve. 
    • Clinical relevance: occlusion of these vessels (typically via a thrombus), results in rapid ischemia and potential necrosis 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)
  • The heart is primarily irrigated during diastole (relaxation of the heart muscle):
    • During systole, the small vessels perforating/supplying the cardiac muscle are compressed.
    • The faster the heart beats = shorter diastole = less time heart has for irrigation
  • Autoregulation: like the brain 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, the heart has the ability to vasodilate and/or vasoconstrict coronary vessels across a range of MAPs to maintain a steady flow rate.
Cardiac irrigation during diastole

Cardiac irrigation during diastole:
During ventricular contraction (systole) flow to cardiac tissue diminishes (down). During ventricular relaxation (diastole), flow to the heart increases.

Image by Lecturio.

Skeletal muscle circulation

Actively contracting muscles increase their own blood flow.

  • 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. General Structure of the Nervous System (SNS):
    • Causes vasoconstriction of arterioles (and thus limits blood flow) in skeletal muscle 
    • Responsible for maintaining arterial blood pressure under resting circumstances
    • Via:
      • Sympathetic nerves
      • Circulating catecholamines (epinephrine and norepinephrine) released from the adrenal medulla
  • Production of local factors causes vasodilation of arterioles and precapillary sphincters:
    • The precapillary sphincters lack innervation → are regulated primarily by production of these local factors
    • Factors include:
      • Lactic acid
      • CO2
      • Adenosine
  • Functional sympatholysis: local factors causing vasodilation overcome any SNS stimulation, resulting in vasodilation during activity.
  • Blood flow to skeletal muscles can increase > 20-fold during strenuous exercise.
  • Like cardiac muscle, flow is restricted during muscle contraction owing to compression of smaller vessels.
  • Isometric contractions cause fatigue more quickly than intermittent isotonic contractions.
    • Isometric contractions: sustained contractions with no change in muscle length
    • Isotonic contractions: change in muscle length producing limb motion

Cutaneous Circulation

Regulating vascular flow to the skin is critical to thermoregulation because heat is dissipated as blood flows near the surface of the skin.

Nonglabrous skin

Nonglabrous skin is thin skin with hair on it.

  • Under stable temperatures: flow is low and stable.
  • In response to systemic cold (i.e., whole-body cold thermal stress): 
    • Sympathetic activation → vasoconstriction → prevents excess heat loss from blood moving too close to the surface 
    • Via epinephrine on α1– and α2-adrenergic receptors
  • In response to local cold:
    • Vasoconstriction is mediated through local translocation of α2c-adrenergic receptors to the cell surface.
    • Not mediated via systemic sympathetic activation
  • In response to systemic heat (i.e., whole-body hot thermal stress): 
    • Release of vasoconstriction
    • Activation of vasodilation → allows more blood near the skin surface to dissipate the heat
    • Via acetylcholine and an unknown molecule (thought to be related to NO, which causes smooth muscle dilation)
  • In response to local heat:
    • Axon reflex: triggers a rapid increase in vasodilation
    • NO: sustains maximal vasodilation

Glabrous skin

Glabrous skin is thicker skin without hair on it (e.g., palms, soles, ear lobes):

  • Tonic sympathetic activation → almost always vasoconstricted, but can be increased
  • Mediated via:
    • Norepinephrine
    • Neuropeptide Y 
  • Has AV anastomoses:
    • Shunts that bypass the capillary beds closer to the surface of the skin
    • Allows for greater amounts of blood flow without loss of heat
  • Glabrous skin has no active vasodilation: flow increases by releasing vasoconstriction.
  • In response to local heat or cold: opening and closing the AV anastomoses allows for alterations in blood flow.
Arteriovenous anastomosis in the dermal layers of glabrous skin

Arteriovenous anastomosis in the dermal layers of glabrous skin, allowing for increased blood flow without loss of heat in these areas
NE: norepinephrine

Image by Lecturio.

Wheal and flare (the triple response)

  • A localized skin response occurring in response to an allergen (e.g., allergy testing and mosquito bites)
  • Wheal (swelling): 
    • 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 and increased blood flow

References

  1. Mohrman, D. E., Heller, L. J. (2018). Overview of the cardiovascular system. Chapter 1 of Cardiovascular Physiology, 9th ed. McGraw-Hill Education. Retrieved November 16, 2021, from accessmedicine.mhmedical.com/content.aspx?aid=1153946098
  2. Mohrman, D. E., Heller, L. J. (2018). Vascular control. Chapter 7 of Cardiovascular Physiology, 9th ed. McGraw-Hill Education. Retrieved November 16, 2021, from accessmedicine.mhmedical.com/content.aspx?aid=1153946722
  3. Klabunde, R. (2020). Skeletal muscle blood flow. Cardiovascular Physiology Concepts. Retrieved November 16, 2021, from https://www.cvphysiology.com/Blood%20Flow/BF015 

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