Overview
Mean arterial pressure (MAP) equations
Mean arterial pressure is the average systemic arterial pressure.
- MAP = (CO x SVR) + CVP
- CO: cardiac output, which = stroke volume x HR
- SVR: systemic vascular resistance
- CVP: central venous pressure (close to 0, often disregarded)
- Can be approximated using systolic and diastolic blood pressures:
- Because the heart spends more time in diastole than in systole, the diastolic blood pressure (DBP) contributes more to the MAP than the systolic blood pressure (SBP).
- Equation: MAP ≅ [ ⅓ (SBP ‒ DBP) ] + DBP
Mean arterial intravascular pressure throughout the cardiac cycle
P: pressure
Factors affecting the mean arterial pressure
Mean arterial pressure is primarily affected by the CO and SVR:
CO = HR x stroke volume:
- HR is determined by:
- ANS (primary regulator) effects on the sinoatrial node in the heart
- Other factors:
- Thyroid hormones Thyroid hormones The 2 primary thyroid hormones are triiodothyronine (T3) and thyroxine (T4). These hormones are synthesized and secreted by the thyroid, and they are responsible for stimulating metabolism in most cells of the body. Their secretion is regulated primarily by thyroid-stimulating hormone (TSH), which is produced by the pituitary gland. Thyroid Hormones
- Circulating catecholamines
- K+ levels
- Ischemia
- Stroke volume is affected by:
- Inotropy: contractile strength of each heartbeat
- Afterload:
- Pressure the left ventricle needs to overcome to eject blood into the aorta
- Closely related to SVR
- Preload (how much the ventricles have stretched/filled with blood by the end of diastole), which is affected by:
- Venous compliance (how much blood 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 can hold)
- Blood volume, primarily affected by renal Na+ and H2O handling
Systemic vascular resistance is primarily affected by:
- Vascular anatomy:
- Arrangement of vessels in series or parallel
- Anatomy of the vessel walls
- Local factors secreted by vessel walls (e.g., NO, prostacyclin, thromboxane), which can cause vasoconstriction and vasodilation
- Neuronal factors:
- Input from the ANS
- Arterial baroreceptor reflex
- Hormones:
- Circulating catecholamines released by the adrenal medulla
- Hormones in the RAAS
- Natriuretic peptides
- Antidiuretic hormone (ADH)
Factors that affect mean arterial pressure (MAP).
CO: cardiac output
SVR: systemic vascular resistance
Regulation by the ANS
Sympathetic stimulation
Sympathetic stimulation increases MAP, which increases both SVR and CO:
- ↑ SVR by inducing vasoconstriction:
- Via α1-adrenergic receptors, which are coupled to Gq proteins
- Uses inositol trisphosphate (IP3) signal transduction → contracts smooth muscle
- ↑ CO by increasing both HR and stroke volume
- Directly, via β1-adrenergic receptors, which increases:
- Contractility (leading to ↑ stroke volume)
- cAMP → ↑ rate of depolarization at the sinoatrial (SA) node) → ↑ HR
- By inducing venoconstriction → forces more blood back to the heart → ↑ preload → ↑ stroke volume → ↑ CO
- By ↑ blood volume through activation of the RAAS → ↑ preload → ↑ stroke volume → ↑ CO
- Directly, via β1-adrenergic receptors, which increases:
Parasympathetic stimulation
Parasympathetic stimulation decreases MAP by decreasing both SVR and CO:
- ↓ SVR by inducing vasodilation
- ↓ CO by decreasing HR
- Via muscarinic M2 receptors which are coupled to Gi proteins
- Leads to ↓ cAMP → ↓ rate of depolarization at the SA node → ↓ HR
Regions of autonomic output regulation
- Hypothalamus Hypothalamus The hypothalamus is a collection of various nuclei within the diencephalon in the center of the brain. The hypothalamus plays a vital role in endocrine regulation as the primary regulator of the pituitary gland, and it is the major point of integration between the central nervous and endocrine systems. Hypothalamus: regulates “automatic” ANS output
- Medulla: coordinates baroreceptor reflex responses (see below)
- Cerebral cortex Cerebral cortex The cerebral cortex is the largest and most developed part of the human brain and CNS. Occupying the upper part of the cranial cavity, the cerebral cortex has 4 lobes and is divided into 2 hemispheres that are joined centrally by the corpus callosum. Cerebral Cortex: adjusts ANS output based on cognitive thought processes (i.e., fear, stress, relaxation)
- Spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: contains sympathetic efferents under reflexive control of the spinal cord
Arterial Baroreceptor Reflex
The baroreceptor reflex is the most important mechanism for acute BP regulation.
Baroreceptors
- Pressure-sensing neurons
- Fire continuously, though firing rate varies depending on the blood pressure
- Location of baroreceptors:
- Carotid sinus:
- Located where the common carotids divide into their internal and external branches
- Innervated by the glossopharyngeal nerve (cranial nerve (CN) IX) nerve
- Aortic arch Aortic arch The branchial arches, also known as pharyngeal or visceral arches, are embryonic structures seen in the development of vertebrates that serve as precursors for many structures of the face, neck, and head. These arches are composed of a central core of mesoderm, which is covered externally by ectoderm and internally by endoderm. Branchial Apparatus and Aortic Arches: innervated by the vagus nerve (CN X)
- Carotid sinus:
Locations of the carotid and aortic baroreceptors
Image by Lecturio.Baroreceptor reflex
- ↑ Blood pressure or blood volume → ↑ vessel stretching
- Baroreceptor nerves ↑ firing frequency when they sense ↑ stretch
- Respond in milliseconds
- Firing rate changes between systole and diastole of a single heartbeat
- Signal sent through afferent fibers → nucleus tractus solitarius in the medulla
- Appropriate response is coordinated in the cardiovascular control centers of the medulla and sent out via ANS fibers
- 3 primary output centers in the cardiovascular control center:
- Sympathetic centers:
- Cardioacceleratory center: ↑ HR and inotropy when activated
- Vasomotor center: ↓ preload and SVR when activated
- Vagal/parasympathetic center:
- Sympathetic centers:
- Cardioinhibitory center: ↓ HR when activated
Baroreceptors are neurons that sense the stretching of a blood vessel.
P: pressure
Example: ↑ blood pressure
↑ Blood pressure → ↑ vessel stretch → ↑ rate of baroreceptor firing → leads to:
- Activation of the vagal/parasympathetic center (i.e., cardioinhibitory center): ↓ HR
- Inhibition of the sympathetic centers (i.e., cardioacceleratory and vasomotor centers):
- ↓ Inotropy
- Venodilation → ↓ preload → ↓ stroke volume → ↓ CO
- Vasodilation → ↓ SVR
- End effect = ↓ blood pressure
Responses of the baroreceptor reflex to increased blood pressure:
HR: heart rate
CO: cardiac output
SVR: systemic vascular resistance
Example: ↓ blood pressure (that is, hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension)
↓ Blood pressure → ↓ stretch → ↓ rate of baroreceptor firing → leads to:
- Inhibition of the vagal/parasympathetic center (i.e., cardioinhibitory center): ↑ HR
- Activation of the sympathetic centers (i.e., cardioacceleratory and vasomotor centers):
- ↑ Inotropy
- Venoconstriction → ↑ preload → ↑ stroke volume → ↑ CO
- Vasoconstriction → ↑ SVR
- End effect = ↑ blood pressure
Responses of the baroreceptor reflex to decreased blood pressure:
HR: heart rate
CO: cardiac output
SVR: systemic vascular resistance
Baroreceptor reflex in response to hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension:
Image by Lecturio.
The decrease in blood pressure is sensed by the aortic baroreceptors, which initiate the reflex. The induced sympathetic response causes peripheral arterial vasoconstriction, increasing systemic vascular resistance (SVR). Constriction of 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 increases preload, which increases stroke volume and thus cardiac output (CO). The sympathetic response also increases HR and cardiac inotropy. These all contribute to normalization of the blood pressure.
MAP: mean arterial pressure
Adjusting baroreceptor function
- Baroreceptors are rapidly adapting → involved only in short-term (i.e., second to second) blood pressure regulation
- Even if baseline blood pressure range is chronically elevated (or lowered), the body still needs to be able to make short-term adjustments to maintain appropriate blood pressure during normal activities (e.g., standing up, walking up stairs).
- Certain situations require the normal range for baroreceptor firing to be “reset” or adjusted .
- The baroreceptor reflex follows a sigmoidal curve:
- Arterial pressure plotted on the x-axis
- Baroreceptor firing frequency plotted on the y-axis
- Highest rate of firing is during the steepest part of the curve
- Effects of chronically elevated blood pressure (e.g., chronic
hypertension
Hypertension
Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter.
Hypertension)
- Shifts the curve to the right
- Baroreceptors do not increase firing rate until higher levels of stretch are sensed.
- Other situations in which baroreflex set point is adjusted for shorter periods of time:
- Aerobic exercise
- Pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
Relationship between arterial pressure and baroreceptor firing frequency in normotensive and hypertensive patients:
As arterial pressure increases, the baroreceptor afferent neurons fire more frequently in a sigmoidal relationship. Chronic
hypertension
Hypertension
Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter.
Hypertension decreases the sensitivity of the baroreceptors, shifting the curve to the right.
MAP: mean arterial pressure
Renin-Angiotensin-Aldosterone System (RAAS)
The RAAS is the major long-term regulator of blood pressure.
Enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body's constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes and hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview in the RAAS
- Renin:
- Secreted by the macula densa cells within 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
- Converts angiotensinogen (secreted by hepatocytes) to angiotensin I
- ACE:
- Secreted by pulmonary vascular endothelium
- Converts angiotensin I to angiotensin II
- Angiotensin II:
- Stimulates release of aldosterone (secreted by the zona glomerulosa in the adrenal cortex)
- ↑ ADH secretion → ↑ renal reabsorption of water
- ↑ Thirst
- ↓ Venous compliance through angiotensin type 1 (AT1) receptors
- Aldosterone:
- Stimulates Na+ and water reabsorption from the renal tubules
- Stimulates excretion of K+ and H+ into the urine
Stimulation of RAAS
Factors that stimulate the RAAS (i.e., renin secretion) include:
- ↓ Renal perfusion:
- ↓ Blood pressure
- ↓ Effective circulating blood volume
- ↓ Sodium delivery to the kidney
- ↑ Sympathetic stimulation
End results of RAAS activation
Renin → angiotensin I → angiotensin II → aldosterone:
- ↑ BP: induces reabsorption of water and Na+, leading to ↑ blood volume → ↑ preload → ↑ stroke volume → ↑ CO → ↑ MAP
- ↑ Serum Na+ (by ↓ urinary excretion of Na+)
- ↓ Serum K+ (by ↑ urinary excretion of K+)
- ↑ Serum pH (by ↑ urinary excretion of H+)
Renin-angiotensin-aldosterone system:
A decrease in mean arterial pressure (MAP) is sensed by the juxtaglomerular apparatus, which then secretes renin. Renin catalyzes the synthesis of angiotensin I which is converted into angiotensin II by ACE. Angiotensin II induces the release of aldosterone from the adrenal cortex, which travels to the distal convoluted tubule, where it causes reabsorption of Na+ and water.
CO: cardiac output
Other Hormones Involved in Arterial Pressure Regulation
Circulating catecholamines
- Circulating catecholamines are secreted by the adrenal medulla directly into the bloodstream
- Catecholamine
hormones
Hormones
Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments.
Hormones: Overview:
- Epinephrine (80%)
- Norepinephrine (20%)
- Effects of catecholamines that ↑ blood pressure:
- Via cardiac β1-adrenergic receptors → ↑ HR and ↑ stroke volume
- Via renal β1-adrenergic receptors → ↑ RAAS → ↑ blood volume
- Via blood vessel α1 receptors → vasoconstriction
- Other effects of catecholamines:
- ↑ Respirations and bronchodilation
- ↑ Blood glucose levels
- ↓ Digestion
- Circulating catecholamines are ↑ by:
- Physical activity
- Stress
- Heart failure
- Shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock
- Pheochromocytoma Pheochromocytoma Pheochromocytoma is a catecholamine-secreting tumor derived from chromaffin cells. The majority of tumors originate in the adrenal medulla, but they may also arise from sympathetic ganglia (also referred to as paraganglioma). Symptoms are associated with excessive catecholamine production and commonly include hypertension, tachycardia, headache, and sweating. Pheochromocytoma
Natriuretic peptides
These hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview act in opposition to the RAAS.
- 2 types of natriuretic peptides:
- Atrial natriuretic peptide (ANP): stored in and released by atrial myocytes
- Brain-type natriuretic peptide (BNP):
- Stored in and released by ventricular myocytes
- Diagnostic marker for heart failure
- ANP and BNP have similar actions:
- ↓ Renin release → ↓ angiotensin II → ↓ aldosterone → diuresis (water loss) and natriuresis (Na+ loss) → ↓ blood volume → ↓ preload → ↓ CO → ↓ MAP
- Minor effects which ↓ CVP and SVR
- Released in response to:
- Atrial distention (most important factor)
- Sympathetic stimulation
- Angiotensin II
- Endothelin
Effects of atrial natriuretic peptide (ANP) on blood volume:
Atrial natriuretic peptide is released by atrial myocytes in response to distention and decreases the release of renin, which results in sodium loss (natriuresis) and water loss (diuresis) in the urine. The loss of volume through the urine decreases central venous pressure (CVP), preload, and systemic vascular resistance (SVR), decreasing blood pressure.
GFR:
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
NEP: neutral endopeptidase
Antidiuretic Hormone (ADH)
- A neuropeptide secreted by the posterior pituitary
- Also called vasopressin
- Secreted in response to:
- Angiotensin II
- Hyperosmolarity
- Sympathetic stimulation
- 2 primary effects:
- At typical levels:
- Action is via vasopressin 2 (V2) receptors
- Stimulates water reabsorption in the renal tubules and collecting system (primary effect) → ↑ blood volume → ↑ preload → ↑ CO → ↑ MAP
- At high levels: vasoconstriction via V1 receptors → ↑ SVR
- At typical levels:
Clinical Relevance
- Hemorrhage: excessive blood loss that results in decreased blood volume, leading to ↓ preload, ↓ stroke volume, ↓ CO, ↓ MAP, and thus ↓ perfusion to vital organs. In order to maintain perfusion, the body will compensate by attempting to increase MAP by boosting CO through increases in HR and contractility, and by vasoconstriction to increase systemic vascular resistance. IV fluids IV fluids Intravenous fluids are one of the most common interventions administered in medicine to approximate physiologic bodily fluids. Intravenous fluids are divided into 2 categories: crystalloid and colloid solutions. Intravenous fluids have a wide variety of indications, including intravascular volume expansion, electrolyte manipulation, and maintenance fluids. Intravenous Fluids and/or blood transfusions can help to restore blood volume.
- Fight-or-flight response: activation of 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), which affects several aspects of the cardiac cycle simultaneously. The SNS activation increases contractility of the heart, while causing vasoconstriction and increasing venous return to the heart. These conditions result in synergistic effects, increasing stroke volume owing to effects on both ↑ preload and ↑ inotropy.
- States of low cardiac output, such as heart failure, 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 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, and cor pulmonale Cor Pulmonale Cor pulmonale is right ventricular (RV) dysfunction caused by lung disease that results in pulmonary artery hypertension. The most common cause of cor pulmonale is chronic obstructive pulmonary disease. Dyspnea is the usual presenting symptom. Cor Pulmonale from severe lung disease may cause abnormally high stimulation of the RAAS in an attempt to maintain adequate arterial pressures. The abnormally high aldosterone, however, may lead to metabolic complications, such as hypokalemia Hypokalemia Hypokalemia is defined as plasma potassium (K+) concentration < 3.5 mEq/L. Homeostatic mechanisms maintain plasma concentration between 3.5-5.2 mEq/L despite marked variation in dietary intake. Hypokalemia can be due to renal losses, GI losses, transcellular shifts, or poor dietary intake. Hypokalemia and/or metabolic alkalosis Metabolic alkalosis The renal system is responsible for eliminating the daily load of non-volatile acids, which is approximately 70 millimoles per day. Metabolic alkalosis also occurs when there is an increased loss of acid, either renally or through the upper GI tract (e.g., vomiting), increased intake of HCO3-, or a reduced ability to secrete HCO3- when needed. Metabolic Alkalosis.
References
- Mohrman, D. E., Heller, L. J. (2018). Overview of the cardiovascular system. Chapter 1 of Cardiovascular physiology, 9th ed. McGraw-Hill Education. accessmedicine.mhmedical.com/content.aspx?aid=1153946098
- Mohrman, D. E., Heller, L. J. (2018). Vascular control. Chapter 7 of Cardiovascular physiology, 9th ed. McGraw-Hill Education. accessmedicine.mhmedical.com/content.aspx?aid=1153946722
- Mohrman, D. E., Heller, L. J. (2018). Regulation of arterial pressure. Chapter 9 of Cardiovascular physiology, 9th ed. McGraw-Hill Education. accessmedicine.mhmedical.com/content.aspx?aid=1153946898
- Baumann, B. M. (2016). Systemic hypertension. Chapter 57 of J. E. Tintinalli, J. S. Stapczynski, O. J. Ma, D. M. Yealy, G. D. Meckler & D. M. Cline (Eds.), Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8th ed. McGraw-Hill Education. accessmedicine.mhmedical.com/content.aspx?aid=1121496251
- Klabunde R. E. (2021). Cardiovascular physiology concepts. Retrieved June 10, 2021, from https://www.cvphysiology.com/
- Saladin, K.S., Miller, L. (2004). Anatomy and physiology, 3rd ed., pp. 753–760. McGraw-Hill Education.
