Color Atlas of Physiology 2003 thieme

A. Schematic view of autonomic nervous system (ANS)

Parasympathetic division		Controlled	Sympathetic division
			(Thoracic and lumbar centers)
(Craniosacral centers)		by
			Transmitter substances:
Transmitter substances:		superordinate
		centers	Preganglionic: Acetylcholine
Preganglionic: Acetylcholine
			Postganglionic: Norepinephrine
Postganglionic: Acetylcholine
			(Exception: Sweat glands,
			some muscular blood vessels)
		III
		VII
		IX
Eye		X	α
			β Eye
		Vagus	α
			Glands

	Glands	nerve
		β
Heart		Heart

Bronchi

Thoracic

Gastrointestinal tract

Lumbar

Ureter

Lower colon

Sacral

Urinary

bladder Genitals

Cholinoceptors

Nicotinic receptors:

–All postganglionic, autonomic ganglia cells and dendrites

–Adrenal medulla

Muscarinic receptors:

–All target organs innervated by postganglionic parasympathetic nerve fibers

(and sweat glands innervated by sympathetic fibers)

		α
		β	Blood vessels
		α
		β	Smooth muscle
			Liver
			Pancreas
			α + β
		Fat and sugar metabolism
		Cholinergic
	β		Sweat glands

α
Genitals
Urinary bladder	Adrenal medulla

Adrenoceptors:

αUsually excitatory (except in GI tract, where

they are indirect relaxants)

βUsually inhibitory (except in heart, where they are excitatory)

β1 mainly in heart

β2 in bronchi, urinary bladder, uterus, gastrointestinal tract, etc.

Postganglionic: Cholinergic

Preganglionic: Cholinergic

Postganglionic: Adrenergic

Plate 3.1 Organization of ANS

79

Despopoulos, Color Atlas of Physiology © 2003 Thieme

All rights reserved. Usage subject to terms and conditions of license.

3 Autonomic Nervous System (ANS)

80

A. Functions of the autonomic nervous system (ANS)

Parasympathetic division (cholinergic)				Controlled by
	Ganglia: NN and M1 receptors
				superordinate centers
	Target organ: M2 oder M3 receptors			(e.g., hypothalamus)
		Eye
		Sphincter pupill.	A	Ganglion
Ganglion sub-		Ciliary muscle	C
				ciliare
mandibulare		Lacrimal glands	A	Ganglion	III
Submandibular					VII
	A			pterygopalatinum
gland			Chorda tympani
	A
Parotid gland					IX
				Ganglion		Cervical
		Heart			X
Activation				oticum
		Slows impulse			1	ganglia
					2
		conduction
Kinin release					3
		Heart rate
				Cervical	4
(sometimes with VIP		Bronchi
					6
Vasodilatation					5
as co-transmitter)		Secretion	A		7
		Musculature	C		8
Watery saliva
					1
		Stomach, intestine			2
					3
		(w/o lower colon
		and rectum)			4
		Tone	A
					5
		Sphincter	R	Thoracic
		Secretion	A		6
					7
		Gallbladder	C		8
					9
Liver		Pancreas			10
					11
Glycogenesis	A
		Exocrine	A		12
		secretion			1
				Lumbar	2
Preganglionic		Ureter	C		3
					4
cholinergic
					5
		Lower colon, rectum
Postganglionic					1
cholinergic		Tone	A
					2
		Secretion	A
					3
		Sphincter	R
					4
				Sacral
Genitals		Urinary bladder			5	Sympathetic
Erection		Detrusor	C	Spinal cord		trunk ganglia
(Vasodilatation)
		Sphincter	R
A = Activation	I = Inhibition		C = Contraction	R = Relaxation		D = Dilatation

Despopoulos, Color Atlas of Physiology © 2003 Thieme

All rights reserved. Usage subject to terms and conditions of license.

Sympathetic division

(Preganglionic cholinergic: NN and M1 receptors,

postganglionic mainly adrenergic)

α receptors (α1: IP3 +DAG

; α2: cAMP

) β receptors (cAMP

)

Eye (α1)

Eye (β2)

Cholinergic

C

Dilator pupillae

Far accommodation

of ciliary muscle

S

A

Sweat glands

Submandibular

Heart (β1 and β2)

gland

Faster stimulus

Postganglionic

Mucus secretion

conduction

sympathetic

A

Heart rate

(viscous)

Myocardial con

-

traction force

Excitability

S	C	Hair muscles
				D	Bronchi (β2)
		of skin
	Stomach, intestine			Stomach, intestine
Ganglion	C	Sphincter (α1)		R	Muscle
coeliacum

		R	Gallbladder
			Kidney
	Pancreas	A	Renin
			secretion (β1)
I	Insulin		Pancreas
	secretion (α2)

			I	Exocrine			A	Insulin
				secretion				secretion (β2)
Ganglion
mesentericum								Blood vessels
			C	Splenic capsule
sup. et inf.					S		D	Skin, muscles,
		S						etc.
				Blood vessels				Lipocytes
			C	In skin	S			Lipolysis
				In muscles
				Coronaries
				General
								Liver (β2 and α1)
				Genitals (α1)			Gluconeogenesis
				Ejaculation
				Urinary bladder			Urinary bladder
			C	Sphincter			R	Detrusor (β2)
			C	Uterus (α1)			R	Uterus (β2)
				(in pregnancy)				(Tocolysis)

S = Efferents from affiliated CNS segment

Blood vessels

S D

Sympathetic cholinergic vasodilatation (not confirmed in humans)

Adrenal medulla

A Secretion

Preganglionic cholinergic

Postganglionic adrenergic

Plate 3.2 u. 3.3 Functions of ANS

81

Despopoulos, Color Atlas of Physiology © 2003 Thieme

All rights reserved. Usage subject to terms and conditions of license.

3 Autonomic Nervous System (ANS)

82

Acetylcholine and Cholinergic

Transmission

Acetylcholine (ACh) serves as a neurotransmitter not only at motor end plates (!p. 56) and in the central nervous system, but also in the autonomic nervous system, ANS (!p. 78ff.), where it is active

in all preganglionic fibers of the ANS;

in all parasympathetic postganglionic nerve endings;

and in some sympathetic postganglionic nerve endings (sweat glands).

Acetylcholine synthesis. ACh is synthesized in the cytoplasm of nerve terminals, and acetyl coenzyme A (acetyl-CoA) is synthesized in mitochondria. The reaction acetyl-CoA + choline is catalyzed by choline acetyltransferase, which is synthesized in the soma and reaches the nerve terminals by axoplasmic transport (!p. 42). Since choline must be taken up from extracellular fluid by way of a carrier, this is the ratelimiting step of ACh synthesis.

Acetylcholine release. Vesicles on presynaptic nerve terminals empty their contents into the synaptic cleft when the cytosolic Ca2+ concentration rises in response to incoming action potentials (AP) (!A, p. 50ff.). Epinephrine and norepinephrine can inhibit ACh release by stimulating presynaptic α2-adrenoceptors (!p. 84). In postganglionic parasympathetic fibers, ACh blocks its own release by binding to presynaptic autoreceptors (M-receptors; see below), as shown in B.

ACh binds to postsynaptic cholinergic receptors or cholinoceptors in autonomic ganglia and organs innervated by parasympathetic fibers, as in the heart, smooth muscles (e.g., of the eye, bronchi, ureter, bladder, genitals, blood vessels, esophagus, and gastrointestinal tract), salivary glands, lacrimal glands, and (sympathetically innervated) sweat glands (!p. 80ff.). Cholinoceptors are nicotinic (N) or muscarinic (M). N-cholinocep- tors (nicotinic) can be stimulated by the alkaloid nicotine, whereas M-cholinoceptors (muscarinic) can be stimulated by the alkaloid mushroom poison muscarine.

Nerve-specific NN-cholinoceptors on autonomic ganglia (!A) differ from musclespecific NM-cholinoceptors on motor end plates (!p. 56) in that they are formed by

different subunits. They are similar in that they are both ionotropic receptors, i.e., they act as cholinoceptors and cation channels at the same time. ACh binding leads to rapid Na+ and Ca2+ influx and in early (rapid) excitatory postsynaptic potentials (EPSP; !p. 50ff.), which trigger postsynaptic action potentials (AP) once they rise above threshold (!A, left panel).

M-cholinoceptors (M1–M5) indirectly affect synaptic transmission through G-proteins (metabotropic receptors).

M1-cholinoceptors occur mainly on autonomic ganglia (!A), CNS, and exocrine gland cells. They activate phospholipase C" (PLC") via Gq protein in the postganglionic neuron. and inositol tris-phosphate (IP3) and diacylglycerol (DAG) are released as second messengers (!p. 276) that stimulate Ca2+ influx and a late EPSP (!A, middle panel). Synaptic signal transmission is modulated by the late EPSP as well as by co-transmitting peptides that trigger peptidergic EPSP or IPSP (!A, right panel).

M2-cholinoceptors occur in the heart and function mainly via a Gi protein (!p. 274 ff.). The Gi protein opens specific K+ channels located mainly in the sinoatrial node, atrioventricular (AV) node, and atrial cells, thereby exerting negative chronotropic and dromotropic effects on the heart (!B). The Gi protein also inhibits adenylate cyclase, thereby reducing Ca2+ influx (!B).

M3-cholinoceptors occur mainly in smooth muscles. Similar to M1-cholinoceptors (!A, middle panel), M3-cholinoceptors trigger contractions by stimulating Ca2+ influx (!p. 70). However, they can also induce relaxation by activating Ca2+-dependent NO synthase, e.g., in endothelial cells (!p. 278).

Termination of ACh action is achieved by acetylcholinesterase-mediated cleavage of ACh molecules in the synaptic cleft (!p. 56). Approximately 50% of the liberated choline is reabsorbed by presynaptic nerve endings (!B).

Antagonists. Atropine blocks all M-cholino- ceptors, whereas pirenzepine selectively blocks M1-cholinoceptors, tubocurarine blocks NM-cholinoceptors (!p. 56), and trimetaphan blocks NN-cholinoceptors.

Despopoulos, Color Atlas of Physiology © 2003 Thieme

All rights reserved. Usage subject to terms and conditions of license.

A. Neurotransmission in autonomic ganglia							Transmission
				Preganglionic
Presynaptic AP		ACh		neuron
	Ca2+
Cholinergic					Peptide as a		Cholinergic
NN-receptor
		Cholinergic		Peptide	co-transmitter
		M1-receptor		receptor
K+		Gq protein	PIP		Postganglionic		and
		Phospholipase Cβ
						neuron	Acetylcholine
Na+ (Ca2+)	IP3	DAG	[Ca]i
20ms Early EPSP		2s	Late EPSP	Peptidergic EPSP or IPSP		60s
mV	mV			mV			Plate 3.4
	Postsynaptic action potentials

B. Cholinergic transmission in the heart
Presynaptic AP		ACh	Postganglionic
			parasympathetic
	Ca2+		neuron
Cholinergic				Choline
M-autoreceptor					Acetate
				Acetylcholine
	Cholinergic			esterase
			K+ channel
	M2-receptor
Adenylyl cyclase	Gi protein	Gi protein
			opens		Sinus node
ATP
				K+	or AV node cell
cAMP			Hyperpolarization
Protein kinase A	Sinus node			AV node
	0			0
Ca2+ influx	mV			mV
	–50			–50
					83
	Negative chronotropism			Negative dromotropism

Despopoulos, Color Atlas of Physiology © 2003 Thieme

All rights reserved. Usage subject to terms and conditions of license.

		Catecholamine, Adrenergic			α2, !1 and !2) can be distinguished according
					to their affinity to E and NE and to numerous
		Transmission and Adrenoceptors
					agonists and antagonists. All adrenoceptors re-
		Certain neurons can enzymatically produce L-			spond to E, but NE has little effect on !2-
		dopa (L-dihydroxyphenylalanine) from the			adrenoceptors. Isoproterenol	(isoprenaline)
		amino acid L-tyrosine. L-dopa is the parent			activates only !-adrenoceptors, and phen-
		substance of	dopamine,	norepinephrine,	tolamine only blocks α-adrenoceptors. The ac-
(ANS)		and epinephrine—the three natural cate-			tivities of all adrenoceptors are mediated by G
		cholamines, which are enzymatically synthe-			proteins (!p. 55).
		sized in this order. Dopamine (DA) is the final			Different subtypes (α1 A, α1 B, α1 D) of α1-
System		step of synthesis in neurons containing only			adrenoceptors can be distinguished (!B1).
		the enzyme required for the first step (the aro-			Their location and function are as follows: CNS
		matic L-amino acid decarboxylase). Dopamine			(sympathetic activity"), salivary glands, liver
Nervous		is used as a transmitter by the dopaminergic			(glycogenolysis"), kidneys (alters threshold
		neurons in the CNS and by autonomic neurons			for renin release; !p. 184),	and smooth
		that innervate the kidney.			muscles (trigger contractions in the arterioles,
		Norepinephrine (NE) is produced when a			uterus, deferent duct, bronchioles, urinary
Autonomic		second enzyme (dopamine-!-hydroxylase) is			bladder, gastrointestinal sphincters, and di-
		also present. In most sympathetic postgan-			lator pupillae).
		glionic nerve endings and noradrenergic central			Activation of α1-adrenoceptors (!B1), me-
		neurons, NE serves as the neurotransmitter			diated by Gq proteins and phospholipase C!
3		along with the co-transmitters adenosine tri-			(PLC!), leads to formation of the second mes-
		phosphate (ATP), somatostatin (SIH), or neu-			sengers inositol tris-phosphate (IP3), which in-
		ropeptide Y (NPY).			creases the cytosolic Ca2+ concentration, and
		Within the adrenal medulla (see below)			diacylglycerol (DAG), which activates protein
		and adrenergic neurons of the medulla ob-			kinase C (PKC; see also p. 276). Gq protein-me-
		longata, phenylethanolamine N-methyltrans-			diated α1-adrenoceptor activity also activates
		ferase transforms norepinephrine (NE) into			Ca2+-dependent K+ channels. The resulting K+
		epinephrine (E).			outflow hyperpolarizes and relaxes target
		The endings of unmyelinated sympathetic			smooth muscles, e.g., in the gastrointestinal
		postganglionic neurons are knobby or varicose			tract.
		(!A). These knobs establish synaptic contact,			Three subtypes (α2 A, α2 B, α2 C) of α2-adreno-
		albeit not always very close, with the effector			ceptors (!B2) can be distinguished. Their lo-
		organ. They also serve as sites of NE synthesis			cation and action are as follows: CNS (sympa-
		and storage. L-tyrosine (!A1) is actively			thetic activity#, e.g., use of the α2 agonist
		taken up by the nerve endings and trans-			clonidine to lower blood pressure), salivary
		formed into dopamine. In adrenergic stimula-			glands (salivation#), pancreatic islets (insulin
		tion, this step is accelerated by protein kinase			secretion#), lipocytes (lipolysis#), platelets
		A-mediated (PKA; !A2) phosphorylation of			(aggregation"), and neurons (presynaptic au-
		the responsible enzyme. This yields a larger			toreceptors, see below). Activated α2-adreno-
		dopamine supply. Dopamine is transferred to			ceptors (!B2) link with Gi protein and inhibit
		chromaffin vesicles, where it is transformed			(via αi subunit of Gi) adenylate cyclase (cAMP
		into NE (!A3). Norepinephrine, the end prod-			synthesis#, !p. 274) and, at the same time, in-
		uct, inhibits further dopamine synthesis			crease (via the !γ subunit of Gi) the open-
		(negative feedback).			probability of voltage-gated K+ channels (hy-
		NE release. NE is exocytosed into the synap-			perpolarization). When coupled with G0 pro-
		tic cleft after the arrival of action potentials at			teins, activated α2-adrenoceptors also inhibit
		the nerve terminal and the initiation of Ca2+ in-			voltage-gated Ca2+ channels ([Ca2+]i#).
		flux (!A4 and p. 50).			All "-adrenoceptors are coupled with a GS
84		Adrenergic	receptors or	adrenoceptors	protein, and its αS subunit releases cAMP as a
		(!B). Four main types of adrenoceptors (α1,			second messenger. cAMP then activates pro-

!

Despopoulos, Color Atlas of Physiology © 2003 Thieme

All rights reserved. Usage subject to terms and conditions of license.

A. Adrenergic transmission
			Activates		Adrenal
			Inhibits		medulla
							Epinephrine (E)
		Varicosities	L-tyrosine					I
							Bloodstream	Transmission
			1
		Inactivated	L-dopa	2		β2-adrenoceptor
								Adrenergic
		(MAO)
	4		Dopamine	cAMP
Action potential
		Ca2+
	7			PKA
		NE	NE			6d		3.5
α2-adrenoceptor							α2-adreno-
			3
Heart, glands,							ceptor	Plate
smooth muscle		6c
			5
6b
Inactivated:		Re-
		absorption
by MAO
by COMT			Norepinephrine				Epinephrine
			(NE)
Capillary
6a
Diffusion into blood
(raises NE in blood)
		α-					β-
		adrenoceptors			β1	adrenoceptors		β2
	α1		α2
!

tein kinase A (PKA), which phosphorylates different proteins, depending on the target cell type (!p. 274).

NE and E work via "1-adrenoceptors (!B3) to open L-type Ca2+ channels in cardiac cell membranes. This increases the [Ca2+]i and therefore produces positive chronotropic, dromotropic, and inotropic effects. Activated Gs protein can also directly increase the open-

probability of voltage-gated Ca2+ channels in the heart. In the kidney, the basal renin secretion is increased via !1-adrenoceptors.

	Activation of "2-adrenoceptors by epineph-
	rine (!B4) increases cAMP levels, thereby
	lowering the [Ca2+]i (by a still unclear mecha-
	nism). This dilates the bronchioles and blood
	vessels of skeletal muscles and relaxes the
	!	85
	muscles of the uterus, deferent duct, and
	!

Despopoulos, Color Atlas of Physiology © 2003 Thieme

All rights reserved. Usage subject to terms and conditions of license.

3 Autonomic Nervous System (ANS)

!

gastrointestinal tract. Further effects of !2- adrenoceptor activation are increased insulin secretion and glycogenolysis in liver and muscle and decreased platelet aggregation. Epinephrine also enhances NE release in noradrenergic fibers by way of presynaptic !2- adrenoceptors (!A2, A5).

Heat production is increased via !3-adreno- ceptors on brown lipocytes (!p. 222).

NE in the synaptic cleft is deactivated by

(!A6 a – d):

diffusion of NE from the synaptic cleft into the blood;

extraneuronal NE uptake (in the heart, glands, smooth muscles, glia, and liver), and subsequent intracellular degradation of NE by catecholamine-O-methyltransferase (COMT) and monoamine oxidase (MAO);

active re-uptake of NE (70%) by the presynaptic nerve terminal. Some of the absorbed NE enters intracellular vesicles (!A3) and is reused, and some is inactivated by MAO;

stimulation of presynaptic α2-adrenocep- tors (autoreceptors; !A 6d, 7) by NE in the synaptic cleft, which inhibits the further release of NE.

Presynaptic α2-adrenoceptors can also be found on cholinergic nerve endings, e.g., in the gastrointestinal tract (motility") and cardiac atrium (negative dromotropic effect), whereas presynaptic M-cholinoceptors are present on noradrenergic nerve terminals. Their mutual interaction permits a certain degree of peripheral ANS regulation.

In alarm reactions, secretion of E (and some NE) from the adrenal medulla increases substantially in response to physical and mental or emotional stress. Therefore, cells not sympathetically innervated are also activated in such stress reactions. E also increases neuronal NE release via presynaptic !2-adrenoceptors (!A2). Epinephrine secretion from the adrenal medulla (mediated by increased sympathetic activity) is stimulated by certain triggers, e.g., physical work, cold, heat, anxiety, anger (stress), pain, oxygen deficiency, or a drop in blood pressure. In severe hypoglycemia (!30 mg/dL), for example, the plasma epinephrine concentration can increase by as much as 20-fold, while the norepinephrine concentration increases by a factor of only 2.5, resulting in a corresponding rise in the E/NE ratio.

The main task of epinephrine is to mobilize stored chemical energy, e.g., through lipolysis and glycogenolysis. Epinephrine enhances the uptake of glucose into skeletal muscle (!p. 282) and activates enzymes that accelerate glycolysis and lactate formation (!p. 72ff.). To enhance the blood flow in the muscles involved, the body increases the cardiac output while curbing gastrointestinal blood flow and activity (!p. 75 A). Adrenal epinephrine and neuronal NE begin to stimulate the secretion of hormones responsible for replenishing the depleted energy reserves (e.g., ACTH; !p. 297 A) while the alarm reaction is still in process.

		Adrenal Medulla
		After stimulation of preganglionic sympa-
		thetic nerve fibers (cholinergic transmission;
		!p. 81), 95% of all cells in the adrenal medulla
		secrete the endocrine hormone epinephrine
		(E) into the blood by exocytosis, and another
		5% release norepinephrine (NE). Compared to
		noradrenergic neurons (see above), NE synthe-
		sis in the adrenal medulla is similar, but most
		of the NE leaves the vesicle and is enzymati-
		cally metabolized into E in the cytoplasm.
		Special vesicles called chromaffin bodies then
		actively store E and get ready to release it and
	86	co-transmitters (enkephalin, neuropeptide Y)
		by exocytosis.

Non-cholinergic, Non-adrenergic

Transmitters

In humans, gastrin-releasing peptide (GRP) and vasoactive intestinal peptide (VIP) serve as co-transmitters in preganglionic sympathetic fibers; neuropeptide Y (NPY) and somatostatin (SIH) are the ones involved in postganglionic fibers. Postganglionic parasympathetic fibers utilize the peptides enkephalin, substance P (SP) and/or NPY as co-transmitters.

Modulation of postsynaptic neurons seems to be the primary goal of preganglionic peptide secretion. There is substantial evidence demonstrating that ATP (adenosine triphosphate), NPY and VIP also function as independent neu-

!

Despopoulos, Color Atlas of Physiology © 2003 Thieme

All rights reserved. Usage subject to terms and conditions of license.

	B. Adrenoceptors
	Norepinephrine			Natural agonists					Epinephrine
	Agonists:	Phenylephrine				Clonidine			Iso-		Salbu-
								proterenol			tamol
											II
	Antagonists:	Prazosin				Yohimbine			Atenolol		Transmission
	receptors:Adrenergic 1	α1		2	α2		3	β1	4	β2
	Gq		Gq	Go		Gi	Gs		Gs		Adrenergic
		PIP2					cAMP		cAMP
					cAMP
	K+		PLCβ
				Ca2+		K+	PKA		PKA
		DAG
		IP3									3.6
					PKA
	PKC										Plate
								Ca2+	?
		Ca2+
	Hyper-	[Ca2+]i		[Ca2+]i		Hyper-	[Ca2+]i		[Ca2+]i
	polarization				polarization
	Inhibition of					α2		β1			β2
	gastrointestinal
	motility	α1		Inhibition of			Drives heart		Dilatation of
			α1	exocytosis
	Contraction of			or secretion					• Vessels
				• Salivary glands					• Bronchioles
	• Blood vessels
									• Uterus
	• Bronchioles			• Insulin
							Renin release		etc.
	• Sphincters			• Norepinephrine
	• Uterus			• Acetylcholine
	etc.			etc.
	!

rotransmitters in the autonomic nervous system. VIP and acetylcholine often occur jointly (but in separate vesicles) in the parasympathetic fibers of blood vessels, exocrine glands, and sweat glands. Within the gastrointestinal tract, VIP (along with nitric oxide) induces the slackening of the circular muscle layer and sphincter muscles and (with the co-transmit- ters dynorphin and galanin) enhances intesti-

nal secretion. Nitric oxide (NO) is liberated from nitrergic neurons (!p. 278)

87

Despopoulos, Color Atlas of Physiology © 2003 Thieme

All rights reserved. Usage subject to terms and conditions of license.

	4		Blood
		Composition and Function of Blood					(e.g., heme) can be protected from breakdown
							and renal excretion. The binding of small
		The blood volume of an adult correlates with					molecules to plasma proteins reduces their
		his or her (fat-free) body mass and amounts to					osmotic efficacy. Many plasma proteins are in-
		ca. 4–4.5 L in women (!) and 4.5–5 L in men of					volved in blood clotting and fibrinolysis.
		70 kg BW ("; !table). The functions of blood					Serum forms when fibrinogen separates from
		include the transport of various molecules (O2,					plasma in the process of blood clotting.
		CO2, nutrients, metabolites, vitamins, electro-					The formationofbloodcells occursinthered
		lytes, etc.), heat (regulation of body tempera-					bone marrow of flat bone in adults and in the
		ture) and transmission of signals (hormones) as					spleen and liver of the fetus. Hematopoietic tis-
		well as buffering and immune defense. The					suescontainpluripotent stemcells which,with
		blood consists of a fluid (plasma) formed el-					the aid of hematopoietic growth factors (see
		ements: Red blood cells (RBCs) transport O2					below), develop into myeloid, erythroid and
		and play an important role in pH regulation.					lymphoid precursor cells. Since pluripotent
		White blood cells (WBCs) can be divided into					stem cells are autoreproductive, their existence
		neutrophilic,			eosinophilic and basophilic		is ensured throughout life. In lymphocyte
		granulocytes, monocytes, and lymphocytes.					development, lymphocytes arising from lym-
		Neutrophils play a role in nonspecific immune					phoid precursor cells first undergo special
		defense, whereas monocytes and lymphocytes					differentiation (in the thymus or bone marrow)
		participate in specific immune responses.					and are later formed in the spleen and lymph
		Platelets (thrombocytes) are needed for he-					nodes as well as in the bone marrow. All other
		mostasis. Hematocrit (Hct) is the volume ratio					precursor cells are produced by myelocytopoie-
		of red cells to whole blood (!C and Table).					sis, that is, the entire process of proliferation,
		Plasma is the fluid portion of the blood in					maturation, and release into the bloodstream
		which electrolytes, nutrients, metabolites, vi-					occurs in the bone marrow. Two hormones, er-
		tamins, hormones, gases, and proteins are dis-					ythropoietin and thrombopoietin, are involved
		solved.					in myelopoiesis. Thrombopoietin			(formed
			Plasma proteins (!Table) are involved in				mainly in the liver) promotes the maturation
		humoral immune defense and maintain on-					and development of megakaryocytes from
		cotic pressure, which helps to keep the blood					which the platelets are split off. A number of
		volume constant. By binding to plasma pro-					othergrowthfactorsaffectbloodcellformation
		teins, compounds insoluble in water can be					in bone marrow via paracrine mechanisms.
		transported in blood, and many substances					Erythropoietin promotes the maturation and
							proliferation of red blood cells. It is secreted by
		Blood volume in liters relative to body weight (BW)
							the liver in the fetus, and chiefly by the kidney
		" 0.041!BW (kg) + 1.53, ! 0.047 !BW (kg) + 0.86					(ca. 90%) in postnatal life. In response to an oxy-
		Hematocrit (cell volume/ blood volume):
							gen deficiency (due to high altitudes, hemoly-
		" 0.40–0.54			Females: 0.37–0.47		sis, etc.; !A), erythropoietin secretion in-
		Erythrocytes (1012/L of blood = 106/ µL of blood):
							creases, larger numbers of red blood cells are
		" 4.6–5.9		! 4.2–5.4			produced, and the fraction of reticulocytes
		Hemoglobin (g/L of blood):
							(young erythrocytes) in the blood rises. The life
		"140–180		! 120–160			span of a red blood cell is around 120 days. Red
		MCH, MCV, MCHC—mean corpuscular (MC), hemo-
							blood cells regularly exit from arterioles in the
		globin (Hb), MC volume, MC Hb concentration !C					splenic pulp and travel through small pores to
		Leukocytes (109/L of blood = 103/ µL of blood):
							enter the splenic sinus (!B), where old red
		3–11 (64% granulocytes, 31% lymphocytes,					blood cells are sorted out		and	destroyed
		6% monocytes)
							(hemolysis). Macrophages in the spleen, liver,
		Platelets (109/L of blood = 103/ µL of blood):
							bone marrow, etc. engulf and break down the
		" 170–360			!180–400
	88						cell fragments. Heme,	the	iron-containing
		Plasma proteins (g/L of serum):
							group of hemoglobin	(Hb)	released during
		66–85 (including 55–64% albumin)
							hemolysis, is broken	down into		bilirubin

(!p. 250), and the iron is recycled (!p. 90).

Despopoulos, Color Atlas of Physiology © 2003 Thieme

All rights reserved. Usage subject to terms and conditions of license.