This document provides information about three main body fluids: blood, lymph, and cerebrospinal fluid (CSF). It describes in detail the composition and functions of blood, including the different blood cells, plasma constituents, coagulation process, and pH regulation. Blood delivers nutrients and oxygen to tissues while removing waste. The coagulation cascade involves platelet activation and two pathways - the tissue factor (extrinsic) pathway and contact activation (intrinsic) pathway - that ultimately result in fibrin formation and clotting. Lymph and CSF are also briefly mentioned.
Energetics
Formation and role of ATP, Creatinine Phosphate and BMR.
References;
Ankur Chaudhari; Pharmaguideline; formation and role of ATP, Creatinine Phosphate; And BMR
https://www.biologyonline.com/tutorials/biological-energy-adp-atp
https://byjus.com/biology/energy-currency-of-the -cell/
https://gbsleiden.com/bioenergetics/
https://www.brainkart.com/article/basal-metabolic-rate-%28BMR%29-the-minimum-energy-expenditure-for-the-body-to-exist_19947/
Energetics
Formation and role of ATP, Creatinine Phosphate and BMR.
References;
Ankur Chaudhari; Pharmaguideline; formation and role of ATP, Creatinine Phosphate; And BMR
https://www.biologyonline.com/tutorials/biological-energy-adp-atp
https://byjus.com/biology/energy-currency-of-the -cell/
https://gbsleiden.com/bioenergetics/
https://www.brainkart.com/article/basal-metabolic-rate-%28BMR%29-the-minimum-energy-expenditure-for-the-body-to-exist_19947/
Factors responsible for erythropoiesis. Development and maturation of erythrocytes require mostly three types of factors
1. General factors 2. Maturation factors 3. Factors necessary for hemoglobin formation.
Blood pressure is the multiply of cardiac output and peripheral resistance.
Blood pressure = Cardiac Output x Peripheral Resistance
Cardiac output is the multi[ply of heart rate and stroke volume.
Normal heart rate in humans is 72 beats/min.
Stroke volume is the volume of blood pumped by heart during one beat.
Cardiac Output = Stroke volume x Heart Rate
Enteric nervous system - GIT physiology, EXTRINSIC AND INTRINSIC NERVE SUPPLY, Meissner's and myenteric's plexus.
local reflex, short reflex. Parasympathetic and sympathetic nerve supply of GIT. Functions of the plexuses.
White blood cells & Immunity (The Guyton and Hall Physiology)Maryam Fida
Leukocytes or WBCs are the mobile units of the body’s immune defense system.
Immunity is the body’s ability to resist or eliminate potentially harmful foreign materials or abnormal cells.
WBC count: 5000 to 11000/ul of blood
GRANULOCYTES
Polymorphonuclear neutrophils 60-70%
Polymorphonuclear eosinophils 2-3%
Polymorphonuclear basophils 0.4%
NON-GRANULOCYTES
Monocytes 5.3%
Lymphocytes 30%
Granulocytes and monocytes are formed and stored only in bone marrow
Lymphocytes and plasma cells are formed and stored mainly in various lymphoid tissue such as lymph node, spleen, thymus and tonsils as well as in bone marrow.
GRANULOCYTES
4 to 8 hours in blood and 4 to 5 days in tissues
MONOCYTES
Monocytes also have a short transit time:
10 to 20 hours in blood and In tissue they swell to much larger size to become tissue macrophages.
LYMPHOCYTES
weeks to months
neutrophil
. 60-70% of leukocytes
nucleus: 2-5 lobes
Counting the number of lobes and grouping them is called Arneth count.
Shift to left means (increase no of young and predominant WBCs) e.g During acute infection.
Shift to right means, old cells are predominant. e.g During recovery phase
NEUTROPENIA
Decrease in neutrophils count
Typhoid
AIDS and viral hepatitis
Kalazar fever
Bone marrow depression by drugs and radiations
NEUTROPHILIA
Increase in neutrophils count
Appendicitis , Tonsillitis, Pneumonia
Burns, Hemorrhage, MI, Pain
Hypoxia, Pregnancy
BASOPHIL
Their cytoplasmic granules take up basic dyes and appear deep blue
MAST CELLS are derived from basophils under the influence of interleukins 3 and 4
Under many allergic conditions basophils and mast cells bursts and releases
Histamine
Bradykinin
Serotonin
Slow reacting substance of anaphylaxis
Heparin
Lysosomal enzymes
It is the capacity of the human body to resist and destroy the invading organisms or toxins.
Factors responsible for erythropoiesis. Development and maturation of erythrocytes require mostly three types of factors
1. General factors 2. Maturation factors 3. Factors necessary for hemoglobin formation.
Blood pressure is the multiply of cardiac output and peripheral resistance.
Blood pressure = Cardiac Output x Peripheral Resistance
Cardiac output is the multi[ply of heart rate and stroke volume.
Normal heart rate in humans is 72 beats/min.
Stroke volume is the volume of blood pumped by heart during one beat.
Cardiac Output = Stroke volume x Heart Rate
Enteric nervous system - GIT physiology, EXTRINSIC AND INTRINSIC NERVE SUPPLY, Meissner's and myenteric's plexus.
local reflex, short reflex. Parasympathetic and sympathetic nerve supply of GIT. Functions of the plexuses.
White blood cells & Immunity (The Guyton and Hall Physiology)Maryam Fida
Leukocytes or WBCs are the mobile units of the body’s immune defense system.
Immunity is the body’s ability to resist or eliminate potentially harmful foreign materials or abnormal cells.
WBC count: 5000 to 11000/ul of blood
GRANULOCYTES
Polymorphonuclear neutrophils 60-70%
Polymorphonuclear eosinophils 2-3%
Polymorphonuclear basophils 0.4%
NON-GRANULOCYTES
Monocytes 5.3%
Lymphocytes 30%
Granulocytes and monocytes are formed and stored only in bone marrow
Lymphocytes and plasma cells are formed and stored mainly in various lymphoid tissue such as lymph node, spleen, thymus and tonsils as well as in bone marrow.
GRANULOCYTES
4 to 8 hours in blood and 4 to 5 days in tissues
MONOCYTES
Monocytes also have a short transit time:
10 to 20 hours in blood and In tissue they swell to much larger size to become tissue macrophages.
LYMPHOCYTES
weeks to months
neutrophil
. 60-70% of leukocytes
nucleus: 2-5 lobes
Counting the number of lobes and grouping them is called Arneth count.
Shift to left means (increase no of young and predominant WBCs) e.g During acute infection.
Shift to right means, old cells are predominant. e.g During recovery phase
NEUTROPENIA
Decrease in neutrophils count
Typhoid
AIDS and viral hepatitis
Kalazar fever
Bone marrow depression by drugs and radiations
NEUTROPHILIA
Increase in neutrophils count
Appendicitis , Tonsillitis, Pneumonia
Burns, Hemorrhage, MI, Pain
Hypoxia, Pregnancy
BASOPHIL
Their cytoplasmic granules take up basic dyes and appear deep blue
MAST CELLS are derived from basophils under the influence of interleukins 3 and 4
Under many allergic conditions basophils and mast cells bursts and releases
Histamine
Bradykinin
Serotonin
Slow reacting substance of anaphylaxis
Heparin
Lysosomal enzymes
It is the capacity of the human body to resist and destroy the invading organisms or toxins.
Forensic Existence of Blood as a Dynamic Evidenceijtsrd
Blood is one of the chief form of biological fluid which is recovered at the location of crime. This review article focus on blood as a prime forensic evidence which is most commonly encountered on crime scenes. The font of insipiration for the same is the variable facts and the frequent occurrence of blood as an evidence on the crime scene. The article pronounces the complete details of blood, including its composition, cell types, relation of blood to scientific science, handling liquid blood stains , wet blood stains, dried blood stains, and the post mortum blood and preservation methods followed by a detailed analysis preliminary and confirmatory test . The analysis of blood can be categorised on the basis of its physical and chemical properties. The major aim of this study is to provide all the relevant facts related to blood collection, packaging and the entire examination. Sanya Sharma | Shipra Rohatgi "Forensic Existence of Blood as a Dynamic Evidence" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-3 | Issue-2 , February 2019, URL: https://www.ijtsrd.com/papers/ijtsrd21396.pdf
Paper URL: https://www.ijtsrd.com/biological-science/cell-biology/21396/forensic-existence-of-blood-as-a-dynamic-evidence/sanya-sharma
1. The concept of the internal environment.
2. Homeostasis. The concept of the norm, hard and plastic constants.Homeokinez.
3. General characteristics of blood. Hematokrit and its clinical evaluation.
4. Functions of blood.
5. The chemical composition of the plasma.
6. Plasma electrolytes and their significance.
It is a brief review on blood and its cellular components. The ppt contains knowledge about types of blood, blood coagulation pathway and disorders of blood.
A brief information about the SCOP protein database used in bioinformatics.
The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.
Cancer cell metabolism: special Reference to Lactate PathwayAADYARAJPANDEY1
Normal Cell Metabolism:
Cellular respiration describes the series of steps that cells use to break down sugar and other chemicals to get the energy we need to function.
Energy is stored in the bonds of glucose and when glucose is broken down, much of that energy is released.
Cell utilize energy in the form of ATP.
The first step of respiration is called glycolysis. In a series of steps, glycolysis breaks glucose into two smaller molecules - a chemical called pyruvate. A small amount of ATP is formed during this process.
Most healthy cells continue the breakdown in a second process, called the Kreb's cycle. The Kreb's cycle allows cells to “burn” the pyruvates made in glycolysis to get more ATP.
The last step in the breakdown of glucose is called oxidative phosphorylation (Ox-Phos).
It takes place in specialized cell structures called mitochondria. This process produces a large amount of ATP. Importantly, cells need oxygen to complete oxidative phosphorylation.
If a cell completes only glycolysis, only 2 molecules of ATP are made per glucose. However, if the cell completes the entire respiration process (glycolysis - Kreb's - oxidative phosphorylation), about 36 molecules of ATP are created, giving it much more energy to use.
IN CANCER CELL:
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
introduction to WARBERG PHENOMENA:
WARBURG EFFECT Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside.
Otto Heinrich Warburg (; 8 October 1883 – 1 August 1970) In 1931 was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme.
WARNBURG EFFECT : cancer cells under aerobic (well-oxygenated) conditions to metabolize glucose to lactate (aerobic glycolysis) is known as the Warburg effect. Warburg made the observation that tumor slices consume glucose and secrete lactate at a higher rate than normal tissues.
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
This presentation explores a brief idea about the structural and functional attributes of nucleotides, the structure and function of genetic materials along with the impact of UV rays and pH upon them.
What is greenhouse gasses and how many gasses are there to affect the Earth.moosaasad1975
What are greenhouse gasses how they affect the earth and its environment what is the future of the environment and earth how the weather and the climate effects.
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
Seminar of U.V. Spectroscopy by SAMIR PANDASAMIR PANDA
Spectroscopy is a branch of science dealing the study of interaction of electromagnetic radiation with matter.
Ultraviolet-visible spectroscopy refers to absorption spectroscopy or reflect spectroscopy in the UV-VIS spectral region.
Ultraviolet-visible spectroscopy is an analytical method that can measure the amount of light received by the analyte.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
Deep Behavioral Phenotyping in Systems Neuroscience for Functional Atlasing a...Ana Luísa Pinho
Functional Magnetic Resonance Imaging (fMRI) provides means to characterize brain activations in response to behavior. However, cognitive neuroscience has been limited to group-level effects referring to the performance of specific tasks. To obtain the functional profile of elementary cognitive mechanisms, the combination of brain responses to many tasks is required. Yet, to date, both structural atlases and parcellation-based activations do not fully account for cognitive function and still present several limitations. Further, they do not adapt overall to individual characteristics. In this talk, I will give an account of deep-behavioral phenotyping strategies, namely data-driven methods in large task-fMRI datasets, to optimize functional brain-data collection and improve inference of effects-of-interest related to mental processes. Key to this approach is the employment of fast multi-functional paradigms rich on features that can be well parametrized and, consequently, facilitate the creation of psycho-physiological constructs to be modelled with imaging data. Particular emphasis will be given to music stimuli when studying high-order cognitive mechanisms, due to their ecological nature and quality to enable complex behavior compounded by discrete entities. I will also discuss how deep-behavioral phenotyping and individualized models applied to neuroimaging data can better account for the subject-specific organization of domain-general cognitive systems in the human brain. Finally, the accumulation of functional brain signatures brings the possibility to clarify relationships among tasks and create a univocal link between brain systems and mental functions through: (1) the development of ontologies proposing an organization of cognitive processes; and (2) brain-network taxonomies describing functional specialization. To this end, tools to improve commensurability in cognitive science are necessary, such as public repositories, ontology-based platforms and automated meta-analysis tools. I will thus discuss some brain-atlasing resources currently under development, and their applicability in cognitive as well as clinical neuroscience.
Comparing Evolved Extractive Text Summary Scores of Bidirectional Encoder Rep...University of Maribor
Slides from:
11th International Conference on Electrical, Electronics and Computer Engineering (IcETRAN), Niš, 3-6 June 2024
Track: Artificial Intelligence
https://www.etran.rs/2024/en/home-english/
Comparing Evolved Extractive Text Summary Scores of Bidirectional Encoder Rep...
Body fluids- CSF, Lymph and Blood
1. BODY FLUIDS: Blood, CSF, Lymph 2017-18
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A lecture notes
on
Body fluids
Blood, Lymph and CSF
By,
K. P. KOMAL
ASSISTANT PROFESSOR
DEPARTMENT OF BIOCHEMISTRY
GOVERNMENT SCIENCE COLLEGE, CHITRADURGA. 577501
KARNATAKA STATE.
,
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Body fluids:
Blood:
Blood is a body fluid in humans and other animals that delivers necessary substances such
as nutrients and oxygen to the cells and transports metabolic waste products away from
those same cells.
In vertebrates, it is composed of blood cells suspended in blood plasma. Plasma, which
constitutes 55% of blood fluid, is mostly water (92% by volume), and contains dissipated
proteins, glucose, mineral ions, hormones, carbon dioxide (plasma being the main
medium for excretory product transportation), and blood cells themselves.
Albumin is the main protein in plasma, and it functions to regulate the colloidal osmotic
pressure of blood. The blood cells are mainly red blood cells (also called RBCs or
erythrocytes), white blood cells (also called WBCs or leukocytes) and platelets (also called
thrombocytes).
The most abundant cells in vertebrate blood are red blood cells. These contain
hemoglobin, an iron-containing protein, which facilitates oxygen transport by reversibly
binding to this respiratory gas and greatly increasing its solubility in blood. In contrast,
carbon dioxide is mostly transported extra cellularly as bicarbonate ion transported in
plasma.
White blood cells help to resist infections and parasites. Platelets are important in the
clotting of blood. Arthropods, using hemolymph, have hemocytes as part of their immune
system.
Blood is circulated around the body through blood vessels by the pumping action of the
heart. In animals with lungs, arterial blood carries oxygen from inhaled air to the tissues
of the body, and venous blood carries carbon dioxide, a waste product of metabolism
produced by cells, from the tissues to the lungs to be exhaled.
Functions
Blood performs many important functions within the body, including:
Supply of oxygen to tissues (bound to hemoglobin, which is carried in red cells)
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Supply of nutrients such as glucose, amino acids, and fatty acids (dissolved in the blood
or bound to plasma proteins (e.g., blood lipids)
Removal of waste such as carbon dioxide, urea, and lactic acid
Immunological functions, including circulation of white blood cells, and detection of
foreign material by antibodies
Coagulation, the response to a broken blood vessel, the conversion of blood from a liquid
to a semisolid gel to stop bleeding
Messenger functions, including the transport of hormones and the signaling of tissue
damage
Regulation of core body temperature
Hydraulic functions
Constituents
Blood accounts for 7% of the human body weight, with an average density around
1060 kg/m3
, very close to pure water's density of 1000 kg/m3
. The average adult has a
blood volume of roughly 5 litres (11 US pt), which is composed of plasma and several
kinds of cells.
These blood cells (which are also called corpuscles or "formed elements") consist of
erythrocytes (red blood cells, RBCs), leukocytes (white blood cells), and thrombocytes
(platelets). By volume, the red blood cells constitute about 45% of whole blood, the
plasma about 54.3%, and white cells about 0.7%.
Human blood fractioned by centrifugation: Plasma (upper, yellow layer), buffy coat
(middle, thin white layer) and erythrocyte layer (bottom, red layer) can be seen.
Cells
One microliter of blood contains:
4.7 to 6.1 million (male), 4.2 to 5.4 million (female) erythrocytes: Red blood cells contain
the blood's hemoglobin and distribute oxygen. Mature red blood cells lack a nucleus and
organelles in mammals. The red blood cells (together with endothelial vessel cells and
other cells) are also marked by glycoproteins that define the different blood types. The
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proportion of blood occupied by red blood cells is referred to as the hematocrit, and is
normally about 45%. The combined surface area of all red blood cells of the human body
would be roughly 2,000 times as great as the body's exterior surface.
4,000–11,000 leukocytes: White blood cells are part of the body's immune system; they
destroy and remove old or aberrant cells and cellular debris, as well as attack infectious
agents (pathogens) and foreign substances. The cancer of leukocytes is called leukemia.
200,000–500,000 thrombocytes: Also called platelets, they take part in blood clotting
(coagulation). Fibrin from the coagulation cascade creates a mesh over the platelet plug.
Plasma
About 55% of blood is blood plasma, a fluid that is the blood's liquid medium, which by
itself is straw-yellow in color. The blood plasma volume totals of 2.7–3.0 liters (2.8–3.2
quarts) in an average human. It is essentially an aqueous solution containing 92% water, 8%
blood plasma proteins, and trace amounts of other materials. Plasma circulates dissolved
nutrients, such as glucose, amino acids, and fatty acids (dissolved in the blood or bound to
Constitution of normal blood
Parameter Value
Hematocrit
45 ± 7 (38–52%) for males
42 ± 5 (37–47%) for females
pH 7.35–7.45
base excess −3 to +3
PO2 10–13 kPa (80–100 mm Hg)
PCO2 4.8–5.8 kPa (35–45 mm Hg)
HCO3
−
21–27 mM
Oxygen saturation
Oxygenated: 98–99%
Deoxygenated: 75%
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plasma proteins), and removes waste products, such as carbon dioxide, urea, and lactic acid.
Other important components include:
Serum albumin
Blood-clotting factors (to facilitate coagulation)
Immunoglobulins (antibodies)
lipoprotein particles
Various other proteins
Various electrolytes (mainly sodium and chloride)
The term serum refers to plasma from which the clotting proteins have been removed. Most
of the proteins remaining are albumin and immunoglobulins.
Blood protein Normal level % Function
Albumins 3.5-5.0 g/dl 55% create and maintain oncotic pressure; transport insoluble molecules
Globulins 2.0-2.5 g/dl 38% participate in immune system
Fibrinogen 0.2-0.45 g/dl 7% Blood coagulation
Regulatory proteins <1%]
Regulation of gene expression
Clotting factors <1%]
Conversion of fibrinogen into fibrin
pH values
Blood pH is regulated to stay within the narrow range of 7.35 to 7.45, making it
slightly basic. Blood that has a pH below 7.35 is too acidic, whereas blood pH above 7.45 is too
basic. Blood pH, partial pressure of oxygen (pO2), partial pressure of carbon dioxide (pCO2), and
bicarbonate (HCO3
−
) are carefully regulated by a number of homeostatic mechanisms, which
exert their influence principally through the respiratory system and the urinary system to
control the acid-base balance and respiration. An arterial blood gas test measures these. Plasma
also circulates hormones transmitting their messages to various tissues.
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Coagulation
Blood coagulation pathways in vivo showing the central role played by thrombin
Coagulation (also known as clotting) is the process by which blood changes from a liquid
to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss
from a damaged vessel, followed by repair. The mechanism of coagulation involves activation,
adhesion, and aggregation of platelets along with deposition and maturation of fibrin. Disorders
of coagulation are disease states which can result in bleeding (hemorrhage or bruising) or
obstructive clotting (thrombosis).
Coagulation is highly conserved throughout biology; in all mammals, coagulation involves
both a cellular (platelet) and a protein (coagulation factor) component. The system in humans
has been the most extensively researched and is the best understood.
Coagulation begins almost instantly after an injury to the blood vessel has damaged the
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endothelium lining the vessel. Leaking of blood through the endothelium initiates two processes:
changes in platelets, and the exposure of subendothilial tissue factor to plasma Factor VII, which
ultimately leads to fibrin formation. Platelets immediately form a plug at the site of injury; this
is called primary hemostasis. Secondary hemostasis occurs simultaneously: Additional
coagulation factors or clotting factors beyond Factor VII respond in a complex cascade to form
fibrin strands, which strengthen the platelet plug.
Physiology
Platelet activation
When the endothelium is damaged, the normally isolated, underlying collagen is exposed
to circulating platelets, which bind directly to collagen with collagen-specific glycoprotein Ia/IIa
surface receptors. This adhesion is strengthened further by von Willebrand factor (vWF), which
is released from the endothelium and from platelets; vWF forms additional links between the
platelets' glycoprotein Ib/IX/V and the collagen fibrils. This localization of platelets to the
extracellular matrix promotes collagen interaction with platelet glycoprotein VI. Binding of
collagen to glycoprotein VI triggers a signaling cascade that results in activation of platelet
integrins. Activated integrins mediate tight binding of platelets to the extracellular matrix. This
process adheres platelets to the site of injury.
Activated platelets will release the contents of stored granules into the blood plasma. The
granules include ADP, serotonin, platelet-activating factor (PAF), vWF, platelet factor 4, and
thromboxane A2 (TXA2), which, in turn, activate additional platelets. The granules' contents
activate a Gq-linked protein receptor cascade, resulting in increased calcium concentration in
the platelets' cytosol. The calcium activates protein kinase C, which, in turn, activates
phospholipase A2 (PLA2). PLA2 then modifies the integrin membrane glycoprotein IIb/IIIa,
increasing its affinity to bind fibrinogen. The activated platelets change shape from spherical to
stellate, and the fibrinogen cross-links with glycoprotein IIb/IIIa aid in aggregation of adjacent
platelets (completing primary hemostasis).
Coagulation cascade
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The coagulation cascade of secondary hemostasis has two initial pathways which lead to
fibrin formation. These are the contact activation pathway (also known as the intrinsic
pathway), and the tissue factor pathway (also known as the extrinsic pathway) which both lead
to the same fundamental reactions that produce fibrin. It was previously thought that the two
pathways of coagulation cascade were of equal importance, but it is now known that the
primary pathway for the initiation of blood coagulation is the tissue factor (extrinsic) pathway.
The pathways are a series of reactions, in which a zymogen (inactive enzyme precursor) of a
serine protease and its glycoprotein co-factor are activated to become active components that
then catalyze the next reaction in the cascade, ultimately resulting in cross-linked fibrin.
Coagulation factors are generally indicated by Roman numerals, with a lowercase a appended
to indicate an active form.
The coagulation factors are generally serine proteases (enzymes), which act by cleaving
downstream proteins. The exceptions are FIII, FV, FVIII, FXIII. FIII, FV and FVIII are
glycoproteins, and Factor XIII is a transglutaminase. The coagulation factors circulate as inactive
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zymogens. The coagulation cascade is therefore classically divided into three pathways. The
tissue factor and contact activation pathways both activate the "final common pathway" of
factor X, thrombin and fibrin.
Tissue factor pathway (extrinsic)
The main role of the tissue factor pathway is to generate a "thrombin burst", a process by
which thrombin, the most important constituent of the coagulation cascade in terms of its
feedback activation roles, is released very rapidly. FVIIa circulates in a higher amount than any
other activated coagulation factor. The process includes the following steps:
1. Following damage to the blood vessel, FVII leaves the circulation and comes into contact
with tissue factor (TF) expressed on tissue-factor-bearing cells (stromal fibroblasts and
leukocytes), forming an activated complex (TF-FVIIa).
2. TF-FVIIa activates FIX and FX.
3. FVII is itself activated by thrombin, FXIa, FXII and FXa.
4. The activation of FX (to form FXa) by TF-FVIIa is almost immediately inhibited by tissue
factor pathway inhibitor (TFPI).
5. FXa and its co-factor FVa form the prothrombinase complex, which activates
prothrombin to thrombin.
6. Thrombin then activates other components of the coagulation cascade, including FV and
FVIII (which forms a complex with FIX), and activates and releases FVIII from being
bound to vWF.
7. FVIIIa is the co-factor of FIXa, and together they form the "tenase" complex, which
activates FX; and so the cycle continues. ("Tenase" is a contraction of "ten" and the suffix
"-ase" used for enzymes.)
Contact activation pathway (intrinsic)
The contact activation pathway begins with formation of the primary complex on
collagen by high-molecular-weight kininogen (HMWK), prekallikrein, and FXII (Hageman
factor). Prekallikrein is converted to kallikrein and FXII becomes FXIIa. FXIIa converts FXI into
FXIa. Factor XIa activates FIX, which with its co-factor FVIIIa form the tenase complex, which
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activates FX to FXa. The minor role that the contact activation pathway has in initiating clot
formation can be illustrated by the fact that patients with severe deficiencies of FXII, HMWK,
and prekallikrein do not have a bleeding disorder. Instead, contact activation system seems to
be more involved in inflammation, and innate immunity. Despite this, interference with the
pathway may confer protection against thrombosis without a significant bleeding risk.
Final common pathway
The division of coagulation in two pathways is mainly artificial, it originates from
laboratory tests in which clotting times were measured after the clotting was initiated by glass
(intrinsic pathway) or by thromboplastin (a mix of tissue factor and phospholipids). In fact
thrombin is present from the very beginning, already when platelets are making the plug.
Thrombin has a large array of functions, not only the conversion of fibrinogen to fibrin, the
building block of a hemostatic plug. In addition, it is the most important platelet activator and
on top of that it activates Factors VIII and V and their inhibitor protein C (in the presence of
thrombomodulin), and it activates Factor XIII, which forms covalent bonds that crosslink the
fibrin polymers that form from activated monomers.
Following activation by the contact factor or tissue factor pathways, the coagulation
cascade is maintained in a prothrombotic state by the continued activation of FVIII and FIX to
form the tenase complex, until it is down-regulated by the anticoagulant pathways.
Cofactors
Various substances are required for the proper functioning of the coagulation cascade:
Calcium and phospholipid
Calcium and phospholipid (a platelet membrane constituent) are required for the tenase
and prothrombinase complexes to function. Calcium mediates the binding of the complexes via
the terminal gamma-carboxy residues on FXa and FIXa to the phospholipid surfaces expressed
by platelets, as well as procoagulant microparticles or microvesicles shed from them. Calcium is
also required at other points in the coagulation cascade.
Vitamin K
Vitamin K is an essential factor to a hepatic gamma-glutamyl carboxylase that adds a
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carboxyl group to glutamic acid residues on factors II, VII, IX and X, as well as Protein S,
Protein C and Protein Z. In adding the gamma-carboxyl group to glutamate residues on the
immature clotting factors Vitamin K is itself oxidized. Another enzyme, Vitamin K epoxide
reductase, (VKORC) reduces vitamin K back to its active form. Vitamin K epoxide reductase is
pharmacologically important as a target of anticoagulant drugs warfarin and related coumarins
such as acenocoumarol, phenprocoumon, and dicumarol. These drugs create a deficiency of
reduced vitamin K by blocking VKORC, thereby inhibiting maturation of clotting factors.
Vitamin K deficiency from other causes (e.g., in malabsorption) or impaired vitamin K
metabolism in disease (e.g., in liver failure) lead to the formation of PIVKAs (proteins formed in
vitamin K absence) which are partially or totally non-gamma carboxylated, affecting the
coagulation factors' ability to bind to phospholipid.
Regulators
Coagulation with arrows for negative and positive feedback.
Five mechanisms keep platelet activation and the coagulation cascade in check. Abnormalities
can lead to an increased tendency toward thrombosis:
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Protein C
Protein C is a major physiological anticoagulant. It is a vitamin K-dependent serine
protease enzyme that is activated by thrombin into activated protein C (APC). Protein C is
activated in a sequence that starts with Protein C and thrombin binding to a cell surface
protein thrombomodulin. Thrombomodulin binds these proteins in such a way that it activates
Protein C. The activated form, along with protein S and a phospholipid as cofactors, degrades
FVa and FVIIIa. Quantitative or qualitative deficiency of either (protein C or protein S) may lead
to thrombophilia (a tendency to develop thrombosis). Impaired action of Protein C (activated
Protein C resistance), for example by having the "Leiden" variant of Factor V or high levels of
FVIII also may lead to a thrombotic tendency.
Antithrombin
Antithrombin is a serine protease inhibitor (serpin) that degrades the serine proteases:
thrombin, FIXa, FXa, FXIa, and FXIIa. It is constantly active, but its adhesion to these factors is
increased by the presence of heparan sulfate (a glycosaminoglycan) or the administration of
heparins (different heparinoids increase affinity to FXa, thrombin, or both). Quantitative or
qualitative deficiency of antithrombin (inborn or acquired, e.g., in proteinuria) leads to
thrombophilia.
Tissue factor pathway inhibitor (TFPI)
Tissue factor pathway inhibitor (TFPI) limits the action of tissue factor (TF). It also
inhibits excessive TF-mediated activation of FVII and FX.
Plasmin
Plasmin is generated by proteolytic cleavage of plasminogen, a plasma protein
synthesized in the liver. This cleavage is catalyzed by tissue plasminogen activator (t-PA), which
is synthesized and secreted by endothelium. Plasmin proteolytically cleaves fibrin into fibrin
degradation products that inhibit excessive fibrin formation.
Prostacyclin
Prostacyclin (PGI2) is released by endothelium and activates platelet Gs protein-linked
receptors. This, in turn, activates adenylyl cyclase, which synthesizes cAMP. cAMP inhibits
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platelet activation by decreasing cytosolic levels of calcium and, by doing so, inhibits the release
of granules that would lead to activation of additional platelets and the coagulation cascade.
Fibrinolysis
Eventually, blood clots are reorganised and resorbed by a process termed fibrinolysis. The main
enzyme responsible for this process (plasmin) is regulated by various activators and inhibitors.
Anticoagulants
Anticoagulants and anti-platelet agents are amongst the most commonly used
medications. Anti-platelet agents include aspirin, dipyridamole, ticlopidine, clopidogrel,
ticagrelor and prasugrel; the parenteral glycoprotein IIb/IIIa inhibitors are used during
angioplasty. Of the anticoagulants, warfarin (and related coumarins) and heparin are the most
commonly used. Warfarin affects the vitamin K-dependent clotting factors (II, VII, IX, X) and
protein C and protein S, whereas heparin and related compounds increase the action of
antithrombin on thrombin and factor Xa. A newer class of drugs, the direct thrombin
inhibitors, is under development; some members are already in clinical use (such as lepirudin).
Also under development are other small molecular compounds that interfere directly with the
enzymatic action of particular coagulation factors (e.g., rivaroxaban, dabigatran, apixaban).
Coagulation factors
Coagulation factors and related substances
Number and/or name Function
Associated genetic
disorders
I (fibrinogen) Forms clot (fibrin)
Congenital
afibrinogenemia, Familial
renal amyloidosis
II (prothrombin)
Its active form (IIa) activates I, V, X, VII,
VIII, XI, XIII, protein C, platelets
Prothrombin G20210A,
Thrombophilia
III (tissue factor or tissue
thromboplastin )
Co-factor of VIIa (formerly known as
factor III)
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IV Calcium
Required for coagulation factors to bind
to phospholipid (formerly known as factor
IV)
V (proaccelerin, labile factor)
Co-factor of X with which it forms the
prothrombinase complex
Activated protein C
resistance
VI Unassigned – old name of Factor Va
VII (stable factor, proconvertin) Activates IX, X
congenital factor VII
deficiency
VIII (Antihemophilic factor A)
Co-factor of IX with which it forms the
tenase complex
Haemophilia A
IX (Antihemophilic factor B or
Christmas factor)
Activates X: forms tenase complex with
factor VIII
Haemophilia B
X (Stuart-Prower factor)
Activates II: forms prothrombinase
complex with factor V
Congenital Factor X
deficiency
XI (plasma thromboplastin
antecedent)
Activates IX Haemophilia C
XII (Hageman factor) Activates factor XI, VII and prekallikrein
Hereditary angioedema
type III
XIII (fibrin-stabilizing factor) Crosslinks fibrin
Congenital Factor XIIIa/b
deficiency
von Willebrand factor Binds to VIII, mediates platelet adhesion von Willebrand disease
prekallikrein (Fletcher factor)
Activates XII and prekallikrein; cleaves
HMWK
Prekallikrein/Fletcher
Factor deficiency
high-molecular-weight kininogen
(HMWK) (Fitzgerald factor)
Supports reciprocal activation of XII, XI,
and prekallikrein
Kininogen deficiency
fibronectin Mediates cell adhesion
Glomerulopathy with
fibronectin deposits
antithrombin III Inhibits IIa, Xa, and other proteases Antithrombin III deficiency
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heparin cofactor II
Inhibits IIa, cofactor for heparin and
dermatan sulfate ("minor antithrombin")
Heparin cofactor II
deficiency
protein C Inactivates Va and VIIIa Protein C deficiency
protein S
Cofactor for activated protein C (APC,
inactive when bound to C4b-binding
protein)
Protein S deficiency
protein Z
Mediates thrombin adhesion to
phospholipids and stimulates degradation
of factor X by ZPI
Protein Z deficiency
Protein Z-related protease
inhibitor (ZPI)
Degrades factors X (in presence of protein
Z) and XI (independently)
plasminogen
Converts to plasmin, lyses fibrin and other
proteins
Plasminogen deficiency,
type I (ligneous
conjunctivitis)
alpha 2-antiplasmin Inhibits plasmin Antiplasmin deficiency
tissue plasminogen activator (tPA) Activates plasminogen
Familial hyperfibrinolysis
and thrombophilia
urokinase Activates plasminogen Quebec platelet disorder
plasminogen activator inhibitor-1
(PAI1)
Inactivates tPA & urokinase (endothelial
PAI)
Plasminogen activator
inhibitor-1 deficiency
plasminogen activator inhibitor-2
(PAI2)
Inactivates tPA & urokinase (placental
PAI)
cancer procoagulant
Pathological factor X activator linked to
thrombosis in cancer
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Lymph
Lymph is the fluid that circulates throughout the lymphatic system. The lymph is
formed when the interstitial fluid (the fluid which lies in the interstices of allbody
tissues) is collected through lymph capillaries. It is then transported through larger
lymphatic vessels to lymph nodes, where it is cleaned by lymphocytes, before emptying
ultimately into the right or the left subclavian vein, where it mixes back with the blood.
Since the lymph is derived from the interstitial fluid, its composition continually
changes as the blood and the surrounding cells continually exchange substances with the
interstitial fluid. It is generally similar to blood plasma, which is the fluid extracellular
matrix (ECM) of whole blood. Lymph returnsproteins and excess interstitial fluid to
the bloodstream. Lymph may pick up bacteria and bring them to lymph nodes, where
they are destroyed. Metastatic cancer cells can also be transported via lymph. Lymph
also transports fats from the digestive system (beginning in the lacteals) to the blood via
chylomicrons.
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The word lymph is derived from the name of the ancient Roman deity of fresh
water, Lympha.
Composition
Lymph has a composition comparable to that of blood plasma, but it may differ
slightly. Lymph contains white blood cells. In particular, the lymph that leaves a lymph
node is richer in lymphocytes. Likewise, the lymph formed in the human digestive
system called chyle is rich in triglycerides (fat), and looks milky white because of its
lipid content.
Formation
Blood supplies nutrients and important metabolites to the cells of a tissue and
collects back the waste products they produce, which requires exchange of respective
constituents between the blood and tissue cells. This exchange is not direct, but instead
is effected through an intermediary called interstitial fluid or tissue fluid, the fluid that
occupies the spaces between the cells and constitutes their immediate environment. As
the blood and the surrounding cells continually add and remove substances from the
interstitial fluid, its composition continually changes. Water and solutes can pass
between the interstitial fluid and blood via diffusion across gaps in capillary walls
called intercellular clefts; thus, the blood and interstitial fluid are in dynamic
equilibrium with each other.
Interstitial fluid forms at the arterial (coming from the heart) end of capillaries
because of the higher pressure of blood compared to veins, and most of it returns to
its venous ends and venules; the rest (up to 10%) enters the lymph capillaries as
lymph. Thus, lymph when formed is a watery clear liquid with the same composition as
the interstitial fluid. However, as it flows through the lymph nodes it comes in contact
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with blood, and tends to accumulate more cells (particularly, lymphocytes) and
proteins.
Lymphatic circulation
Tubular vessels transport lymph back to the blood, ultimately replacing the
volume lost during the formation of the interstitial fluid. These channels are the
lymphatic channels, or simply lymphatics.
Unlike the cardiovascular system, the lymphatic system is not closed and has no
central pump, or lymph hearts (which are found in some animals). Lymph transport,
therefore, is slow and sporadic. Despite low pressure, lymph movement occurs due
to peristalsis (propulsion of the lymph due to alternate contraction and relaxation
of smooth muscle tissue), valves, and compression during contraction of adjacent
skeletal muscle and arterial pulsation.
Lymph that enters the lymph vessels from the interstitial spaces usually does not
flow backwards along the vessels because of the presence of valves. If
excessive hydrostatic pressure develops within the lymph vessels, though, some fluid can
leak back into the interstitial spaces and contribute to formation of oedema.
Flow of the lymph in the thoracic duct in an average resting person usually
approximates 100ml per hour. Accompanied by another ~25ml per hour in other
lymph vessels, total lymph flow in the body is about 4 to 5 liters per day. This can be
elevated several folds while exercising. Thus it can be estimated that without lymphatic
flow, an average resting person would die within 24 hours.
Cerebrospinal fluid
Cerebrospinal fluid (CSF) is a clear, colorless body fluid found in the brain
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and spinal cord. It is produced in the choroid plexuses of the ventricles of the brain, and
absorbed in the arachnoid granulations. There is about 125mL of CSF at any one time,
and about 500mL is generated every day. CSF acts as a cushion or buffer for the brain,
providing basic mechanical and immunological protection to the brain inside the skull.
The CSF also serves a vital function in cerebral autoregulation of cerebral blood flow.
The CSF occupies the subarachnoid space (between the arachnoid mater and
the pia mater) and the ventricular system around and inside the brain and spinal cord.
It fills the ventricles of the brain, cisterns, and sulci, as well as thecentral canal of the
spinal cord. There is also a connection from the subarachnoid space to the bony
labyrinth of the inner ear via the perilymphatic duct where the perilymph is continuous
with the cerebrospinal fluid.
Circulation
There is about 125-150 mL of CSF at any one time. This CSF circulates within
the ventricular system of the brain. The ventricles are a series of cavities filled with CSF.
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The majority of CSF is produced from within the two lateral ventricles. From here, the
CSF passes through the interventricular foramina to the third ventricle, then the
cerebral aqueduct to the fourth ventricle. From the fourth ventricle, the fluid passes
into the subarachnoid space through four openings – the central canal of the spinal
cord, the median aperture, and the two lateral apertures. CSF is present within the
subarachnoid space, which covers the brain, spinal cord, and stretches below the end of
the spinal cord to the sacrum. There is a connection from the subarachnoid space to
the bony labyrinth of the inner ear making the cerebrospinal fluid continuous with
the perilymph in 93% of people.
CSF moves in a single outward direction from the ventricles, but
multidirectionally in the subarachnoid space. Fluid movement is pulsatile, matching the
pressure waves generated in blood vessels by the beating of the heart. Some authors
dispute this, posing that there is no unidirectional CSF circulation, but cardiac cycle-
dependent bi-directional systolic-diastolic to-and-fro cranio-spinal CSF movements.
Contents
The CSF is derived from blood plasma and is largely similar to it, except that CSF
is nearly protein-free compared with plasma and has some different electrolyte levels.
Owing to the way it is produced, CSF has a higher chloride level than plasma, and an
equivalent sodium level.
CSF contains approximately 0.3% plasma proteins, or approximately 15 to
40 mg/dL, depending on sampling site. In general, globular proteins and albumin are in
lower concentration in ventricular CSF compared to lumbar or cisternal fluid. This
continuous flow into the venous system dilutes the concentration of larger, lipid-
insoluble molecules penetrating the brain and CSF. CSF is normally free of red blood
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cells, and at most contains only a few white blood cells. Any white blood cell
count higher than this constitutes pleocytosis.
Function
CSF serves several purposes:
1. Buoyancy: The actual mass of the human brain is about 1400–1500 grams;
however, the net weight of the brain suspended in the CSF is equivalent to a
mass of 25-50 grams. The brain therefore exists in neutral buoyancy, which
allows the brain to maintain its density without being impaired by its own
weight, which would cut off blood supply and kill neurons in the lower sections
without CSF.
2. Protection: CSF protects the brain tissue from injury when jolted or hit, by
providing a fluid buffer that acts as a shock absorber from some forms of
mechanical injury.
3. Prevention of brain ischemia: The prevention of brain ischemia is made by
decreasing the amount of CSF in the limited space inside the skull. This decreases
total intracranial pressure and facilitates blood perfusion.
4. Homeostasis: CSF allows for regulation of the distribution of substances between
cells of the brain, and neuroendocrine factors, to which slight changes can cause
problems or damage to the nervous system. For example, high
glycine concentration disrupts temperature and blood pressure control, and high
CSF pH causes dizziness and syncope.
5. Clearing waste: CSF allows for the removal of waste products from the brain, and
is critical in the brain's lymphatic system. Metabolic waste products diffuse
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rapidly into the CSF and are removed into the bloodstream as CSF is absorbed.
Production
Comparison of Average Serum and Cerebrospinal Fluid
Substance CSF Serum
Water Content (%) 99 93
Protein (mg/dL) 35 7000
Glucose (mg/dL) 60 90
Osmolarity (mOsm/L) 295 295
Sodium (mEq/L) 138 138
Potassium (mEq/L) 2.8 4.5
Calcium (mEq/L) 2.1 4.8
Magnesium (mEq/L) 2.0–2.5 1.7
Chloride (mEq/L) 119 102
pH 7.33 7.41
The brain produces roughly 500 mL of cerebrospinal fluid per day, at a rate of
about 25 mL an hour. This transcellular fluid is constantly reabsorbed, so that only
125–150 mL is present at any one time.
Most (about two-thirds to 80%) of CSF is produced by the choroid plexus. The
choroid plexus is a network of blood vessels present within sections of thefour
ventricles of the brain. It is present throughout the ventricular system except for
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the cerebral aqueduct, frontal horn of the lateral ventricle, and occipital horn of the
lateral ventricle. CSF is also produced by the single layer of column-shaped ependymal
cells which line the ventricles; by the lining surrounding the subarachnoid space; and a
small amount directly from the tiny spaces surrounding blood vessels around the brain.
CSF is produced by the choroid plexus in two steps. Firstly, a filtered form of
plasma moves from fenestrated capillaries in the choroid plexus into an interstitial
space, with movement guided by a difference in pressure between the blood in the
capillaries and the interstitial fluid. This fluid then needs to pass through
the epithelium cells lining the choroid plexus into the ventricles, an active process
requiring the transport of sodium, potassium and chloride that draws water into the
CSF by creating osmotic pressure. Unlike blood passing from the capillaries into the
choroid plexus, the epithelial cells lining the choroid plexus contain tight
junctions between cells, which act to prevent most substances flowing freely into the
CSF.
Water and carbon dioxide from the interstitial fluid diffuse into the epithelial cells.
Within these cells, carbonic anhydrase converts the substances into bicarbonate and
hydrogen ions. These are exchanged for sodium and chloride on the cell surface facing
the interstitium. Sodium, chloride, bicarbonate and potassium are then actively secreted
into the ventricular lumen. This creates osmotic pressure and draws water into the
CSF, facilitated by aquaporins. Chloride, with a negative charge, moves with the
positively charged sodium, to maintain electroneutrality. Potassium and bicarbonate are
also transported out of the CSF. As a result, CSF contains a higher concentration of
sodium and chloride than blood plasma, but less potassium, calcium and glucose and
protein. Choroid plexuses also secrete growth factors, vitamins B1,12 C, folate, beta-2
microglobulin, arginine vasopressin and nitrous oxide into the CSF. A Na-K-Cl
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cotransporter and Na/K ATPase found on the surface of the choroid endothelium,
appears to play a role in regulating CSF secretion and composition.
Reabsorption
CSF returns to the vascular system by entering the dural venous
sinuses via arachnoid granulations. These are outpouchings of the arachnoid mater into
the venous sinuses around the brain, with valves to ensure one-way drainage.This occurs
because of a pressure difference between the arachnoid mater and venous sinuses. CSF
has also been seen to drain into lymphatic vessels, particularly those surrounding the
nose via drainage along the olfactory nerve through the cribriform plate. The pathway
and extent are currently not known, but may involve CSF flow along some cranial
nerves and be more prominent in the neonate. CSF turns over at a rate of three to four
times a day. CSF has also been seen to be reabsorbed through the sheathes
of cranial and spinal nerve sheathes, and through the ependyma.
Regulation
The composition and rate of CSF generation are influenced by hormones and the
content and pressure of blood and CSF. For example, when CSF pressure is higher, there
is less of a pressure difference between the capillary blood in choroid plexuses and the
CSF, decreasing the rate at which fluids move into the choroid plexus and CSF
generation. The autonomic nervous system influences choroid plexus CSF secretion, with
activation of the sympathetic nervous system increasing secretion and
the parasympathetic nervous system decreasing it. Changes in the pH of the blood can
affect the activity of carbonic anhydrase, and some drugs (such as frusemide, acting on
the Na-K-Cl cotransporter) have the potential to impact membrane channels.