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Histology-smooth muscle

Authors: Rajaguru Paramaguru, M.D., Rola H. Ali, M.D.

Editorial Board Member: Josephine K. Dermawan, M.D., Ph.D.

Last staff update: 5 September 2023 (update in progress)

Copyright: 2023, PathologyOutlines.com, Inc.

PubMed Search: Histology smooth muscle

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Table of Contents

Cite this page: Paramaguru R, Ali RH. Histology-smooth muscle. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/softtissuesmoothmuscle.html. Accessed September 25th, 2023.

Definition / general

Nonstriated muscle that serves diverse functions throughout the body and is responsible for involuntary movements
1 of 3 types of muscle tissue alongside cardiac and skeletal muscle

Essential features

Smooth muscle is widely distributed throughout the body and serves diverse functions
Physiologically divided into single unit and multi unit fibers
Intracellular actin and myosin filaments generate contractile forces by a sliding filament mechanism
Contractile filaments are not arranged into sarcomeres, thus giving it a nonstriated (smooth) appearance
Awareness of the distribution of smooth muscle helps avoid microscopic misinterpretation

Terminology

Synonyms: nonstriated muscle, involuntary muscle
Smooth pertains to the lack of striations
Muscle fiber is the basic functional unit (also known as myocyte, myofiber, muscle cell)
Myofilaments are the contractile apparatus of smooth muscle cells consisting of thick myosin filaments and thin actin filaments along with regulatory proteins

Embryogenesis

Smooth muscle is derived from mesoderm and neural crest cells
Heterogeneity of smooth muscle origins in vascular development provides insights into the pathophysiology and site specific localization of some vascular disorders (e.g., atherosclerosis)
References: StatPearls: Physiology, Smooth Muscle [Accessed 3 July 2023], Cell Mol Life Sci 2014;71:2271

Functional anatomy

Smooth musculature is ubiquitous in viscera and blood vessels
At certain sites, smooth and skeletal muscles come into contact coordinating the contractile force and direction with each other (e.g., esophagus, rectum and pelvic floor) (Anat Sci Int 2023;98:407)
Muscle cell spatial arrangements (J Smooth Muscle Res 2021;57:19)
- Circumferential ring arrangement (e.g., arterioles)
- Less circumferential and not as tightly packed bundles (e.g., ureter, bile duct)
- Orthogonal layers (e.g., intestine, vas deferens, vessels)
- Cord-like (e.g., teniae coli)
- Bundles running seemingly in all directions (e.g., urinary bladder, myometrium)
- Laminar sheet (e.g., trachea)
- Short straight bundles (e.g., arrector pili)
Contractile properties serve diverse functions based on
- Dimensions of the muscle fibers
- Spatial arrangement of the fibers (above)
- Types of stimuli
- Characteristics of innervation
Types of intracellular filaments
- Thin actin, contractile function
- Thick myosin, contractile function
- Intermediate desmin and vimentin, maintain structure
Visceral smooth muscle: gamma smooth muscle actin and desmin predominate
Vascular smooth muscle: abundant alpha smooth muscle actin, vimentin > desmin (Proc Natl Acad Sci U S A 1981;78:298)

Skin

Arrector pili muscles	Located in the dermis inserting into hair follicles below sebaceous glands causing piloerection Mediate thermoregulation and contribute to follicular unit integrity and sebum secretion (Int J Trichology 2014;6:88)
Nipple	Smooth muscle bundles present in areola and around lactiferous ducts For nipple erection and milk expression
Scrotum	Tunica dartos in subdermal layer Assists in scrotal thermoregulation
Vulva	Smooth muscle in the dermis of the labia majora May represent vestigial homologue to male dartos muscle (Am J Obstet Gynecol 2022;227:105)

Eye

Iris	Smooth muscle fibers function to regulate the pupil diameter controlling the amount of light entering the lens
Ciliary body	Ciliary muscle helps to control the shape of the lens (accommodation)
Müller muscle of eyelid	Also known as superior tarsal muscle; small bundles of smooth muscle within the upper eyelid adjoining the levator palpebrae superioris to help keep the eyes open (Ann Plast Surg 1985;14:324)
Orbit	Fibrous septa of the orbit, important for support and motion of the globe, may contain smooth muscle bundles (Acta Morphol Neerl Scand 1982;20:293)

Cardiovascular

Elastic arteries	Tunica media: more elastic fibers and less smooth muscle relative to muscular arteries Conducting blood and withstanding the high pressure of blood ejected from the heart (e.g., aorta, pulmonary arteries)
Muscular arteries	Tunica media: less elastic fibers and more smooth muscle relative to elastic arteries Constrict and dilate as needed to change the amount of blood delivered (e.g., radial artery, femoral artery)
Arterioles	Composed chiefly of smooth muscle; critical in maintaining systemic vascular resistance and determining blood pressure
Capillaries	Composed of a single endothelial layer and a pericytic layer (see below) allowing for diffusion of nutrients and oxygen
Venules	Only 1 or 2 layers of muscle also allow for diffusion
Veins	Less smooth muscle and connective tissue than arteries making their walls thinner and allowing them to accommodate a large volume of blood at relatively low pressures
Capillary pericytes	Pericytes are essentially smooth muscle cells that contain a large number of filaments; they are involved in the regulation of blood flow and maintenance of tissue specific functions such as the blood brain barrier (Neuro Oncol 2005;7:452, Mills: Histology for Pathologists, 5th Edition, 2019)
Lymphatics	Larger lymphatics have thin wisps of muscular media
Endocardium	Often contains a rudimentary layer of smooth muscle which should not be mistaken for Purkinje cells or conduction system tracts (Lindberg: Diagnostic Pathology - Normal Histology, 3rd Edition, 2022)

Lung

Conducting airways	Smooth muscle present in the walls of the airways from trachea to terminal bronchioles, becoming progressively less prominent distally, serving to regulate the bronchomotor tone of the airways (Int J Biochem Cell Biol 2003;35:272) In the rigid trachea, the muscle may have a passive role, completing the circumference of the tube (J Smooth Muscle Res 2021;57:19)
Respiratory airways	Bundles of smooth muscle can be seen at the level of the alveolar ducts, interrupted by alveolar openings, which may appear as isolated round or oblong aggregates in cross section

Gastrointestinal

Muscularis mucosae	Thin muscular layer between mucosa and submucosa Layers: inner circular and outer longitudinal (inconspicuous on H&E) except in the esophagus where it is only longitudinal Thickest in distal esophagus In the rectum it extends into the upper transition zone of the anal canal Provides a structural foundation for the mucosa and keeps the glands in constant motion to expel their contents
Muscularis propria (externa)	Thick muscular layer between submucosa and subserosa / serosa Layers: inner circular and outer longitudinal except in the stomach where there is an additional innermost oblique layer In the esophagus: upper part is entirely skeletal muscle, middle part is a mixture of skeletal and smooth, lower part is entirely smooth Contains the myenteric plexus of Auerbach and interstitial cells of Cajal responsible for peristaltic movement Teniae coli are 3 longitudinal smooth muscle bands in the colonic wall
Anal canal	Internal anal sphincter is a thickened extension of the circular smooth muscle in the bowel wall
Pelvic floor and perineum	Perineal smooth muscle: the rectourethralis in men and the rectovaginalis in women are considered homologous structures contributing to the stabilization of the pelvic floor (Anat Sci Int 2023;98:407)

Biliary system

Gallbladder	Muscularis propria: loosely arranged bundles of circular, longitudinal and oblique fibers, lying directly beneath the lamina propria (no muscularis mucosae or submucosa)
Extrahepatic biliary tract	Lacks smooth muscle except for common bile duct (particularly the lower one - third) and cystic duct at junction with gallbladder (also known as the spiral valve of Heister), serving to prevent overdistention or collapse of the cystic duct (Mills: Histology for Pathologists, 5th Edition, 2019, Lindberg: Diagnostic Pathology - Normal Histology, 3rd Edition, 2022)
Sphincter of Oddi	Concentric ring of muscle regulating the flow of bile and pancreatic secretions into the duodenum and preventing reflux of duodenal contents

Genitourinary

Bladder	Muscularis mucosae: discontinuous wisps of smooth muscle Muscularis propria (detrusor muscle): 3 coats with interwoven orientation, inner and outer longitudinal and a central circular, which seem to be randomly arranged Detrusor contributes to micturition and allows the bladder to stretch for the storage of urine
Ureter	Muscularis propria with indistinct layers
Renal pelvis	Muscularis propria becomes thinner along the major and minor calyces
Male ducts & seminal vesicles	Efferent ductules, epididymis and vas deferens all contain smooth muscle which function to propel sperm and fluids Thickest in vas deferens (inner and outer longitudinal layers and middle circular), which transports spermatozoa from epididymis to ejaculatory duct Seminal vesicles are also surrounded by a prominent layer of smooth muscle
Penis	Corpora cavernosa: main erectile tissues of the penis consisting of anastomosing vascular network with intervening smooth muscle and fibrous tissue Corpus spongiosum surrounds the penile urethra with less smooth muscle than that of the cavernosa Penile dartos surrounds the penile shaft and is continuous with the scrotal dartos producing retraction of genital structures when exterior temperature falls
Prostate	Anterior fibromuscular stroma constitutes the anterior nonglandular portion of the prostatic surgical capsule, composed of vertically oriented smooth muscle continuous with the bladder detrusor muscle, may play a role in maintaining urethral resistance (Urology 2010;76:511.e10) Prostate itself has abundant fibromuscular stroma
Urethra	Internal urethral sphincter: collar of smooth muscle at the neck of the bladder continuous with the detrusor muscle of bladder Maintains urinary continence and prevents reflux of semen into the bladder

Female reproductive

Uterus	Smooth muscle within the corpus is more concentrated than the muscle in either the cervix or the lower uterine segment This distribution of muscle is consistent with the passive role of the cervix during parturition
Vagina	Smooth muscle musculature is continuous with that of the uterus
Fallopian tube	Smooth muscle is thickest in the isthmus and thins as the fimbriated end is approached Remainder of tube wall contains 2 layers of smooth muscle
Ovary	Occasional smooth muscle may be identified within the stroma

References: Mills: Histology for Pathologists, 5th Edition, 2019, Lindberg: Diagnostic Pathology - Normal Histology, 3rd Edition, 2022

Physiology

2 major types of smooth muscle
- Single unit
  - Hundreds to thousands of muscle fibers contract together as a single unit
  - Action potential spreads through gap junctions between fibers
  - Controlled by nervous and nonnervous stimuli
  - Examples: walls of viscera such as gastrointestinal tract, blood vessels
- Multi unit
  - Each fiber is innervated by a single nerve ending and operates independently for much finer control
  - Controlled by nervous stimuli
  - Examples: ciliary muscle of the eye, arrector pili muscles
Types of stimuli
- Nervous: autonomic
- Nonnervous: hormones, local tissue chemical factors, stretch of the fibers (mechanical)
Mechanism of contraction
- Initiated by an increase in intracellular Ca²⁺ ions upon stimulation (as in skeletal muscle)
- Mediated by actin myosin filament interaction (as in skeletal muscle)
- Does not involve troponin (unlike skeletal muscle)
- Source of Ca²⁺ ions
  - Entry through channels in the caveolae of the cell membrane
  - Release of sequestered Ca²⁺ from the sarcoplasmic (endoplasmic) reticulum
- Ca²⁺ binds to calmodulin (regulatory protein in place of troponin)
  - Calmodulin calcium complex → activation of myosin light chain kinase (MLCK) → phosphorylation of myosin light chain → myosin actin interaction → contraction
Some differences from skeletal muscle
- Involuntary contractions
- Prolonged and slower yet stronger contractions
- Less energy consumption
- Nervous and nonnervous stimuli
References: Hall: Guyton and Hall Textbook of Medical Physiology, 13th Edition, 2015, StatPearls: Physiology, Smooth Muscle [Accessed 3 July 2023]

Diagrams / tables

Contributed by Rola H. Ali, M.D.

Smooth muscle fiber structure

Contractile proteins relevant to IHC

Microscopic (histologic) description

Cell size: diameter between 1 - 5 μm and length between 20 - 500 μm (much smaller than skeletal muscle)
Cell shape: spindle shaped or fusiform with tapered ends
Cytoplasm: eosinophilic fibrillar with distinct cell borders and no cross striations
Nucleus
- Central elongated cigar shaped nucleus with blunted ends
- Spiral corkscrew appearance in the contracted state
- Appear round on cross section
Spindle cell mimics
- Fibroblasts in dense regular connective tissue
- Myofibroblasts: spindle to stellate, amphophilic cytoplasm, single elongated nucleus with 1 or 2 small nucleoli, collagen in between the cells
- Schwann cells: cells show slightly undulated buckled nuclei, often with 1 blunt and 1 pointed end, described as S shaped, serpentine, comma shaped, bullet shaped or boomerang-like
Reference: Young: Wheater's Functional Histology, 6th Edition, 2013

Microscopic (histologic) images

Contributed by Rola H. Ali, M.D.

Relaxed smooth muscle fibers

Contracted smooth muscle

Spiral corkscrew nuclei

Cross versus longitudinal sections

Smooth versus skeletal muscle

Smooth muscle versus nerve

Myofibroblasts for comparison

Virtual slides

Images hosted on other servers:

Gallbladder muscularis beneath lamina

Juxtaposition of smooth and skeletal esophagus

Positive stains

Smooth muscle actin (SMA): diffuse cytoplasmic staining (as opposed to membranous tram track in myofibroblasts)
Muscle specific actin (HHF35): panmuscle marker
Desmin: panmuscle marker
h-caldesmon: actin binding protein
Calponin: actin binding protein
Smooth muscle myosin heavy chain (SMMHC)
Smoothelin: terminally differentiated smooth muscle cells (Am J Surg Pathol 2009;33:1795)
Masson trichrome: smooth muscle stains red

Negative stains

MyoD1, myogenin, myoglobin

Electron microscopy description

Cytoplasm
- Filaments
  - Thin (actin) and thick (myosin) filaments
  - Intermediate filaments
- Dense bodies
  - Electron opaque structures floating freely within the cytoplasm → analogous to Z lines of striated muscle anchoring actin and myosin
- Organelles
  - Include sarcoplasmic reticulum, mitochondria and Golgi apparatus
Cell membrane
- Membrane bound dense bodies
- Pinocytotic vesicles or caveolae → Ca²⁺ movement across the membrane
- Gap junctions → consist of connexins facilitating the transfer of metabolites, ions and signaling molecules
References: Edwin: Methods in Pharmacology - Smooth Muscle, 1st Edition, 1975, Motta: Ultrastructure of Smooth Muscle, 1st Edition, 1990

Electron microscopy images

Images hosted on other servers:

Smooth muscle longitudinal section

Smooth muscle cross section

Wall of muscular artery

Intestinal muscularis propria (externa)

Smooth muscle cross section

Videos

Smooth muscle versus myofibroblasts

Board review style question #1

Which immunohistochemical expression pattern is expected to be seen in the tissue shown above?

Cytoplasmic staining with h-caldesmon
Cytoplasmic staining with myogenin
Membranous staining with smooth muscle actin
Nuclear and cytoplasmic staining with S100
Nuclear staining with MyoD1

Board review style answer #1

A. Cytoplasmic staining with h-caldesmon. Smooth muscle cells contain cytoplasmic caldesmon molecules bound to actin filaments. Answers B and E are incorrect because myogenin and MyoD1 both encode nuclear proteins expressed in skeletal muscle. Answer C is incorrect because membranous staining with smooth muscle actin is seen in myofibroblasts. Answer D is incorrect because S100 staining is seen in Schwann cells.

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Reference: Histology-smooth muscle

Board review style question #2

Which of the following statements pertaining to the physiology of smooth muscle contraction is true?

Actin filaments pull the Z lines inward in the contracted state
Ca²⁺ binding to calmodulin stimulates myosin actin interaction
Consumption of tremendous amounts of ATP is required
Contraction is stimulated by somatic motor neurons
Strong affinity of troponin for Ca²⁺ ions initiates contractions

Board review style answer #2

B. Ca²⁺ binding to calmodulin stimulates myosin actin interaction. In smooth muscle, calmodulin acts in place of troponin. Answers A and C - E are incorrect because these statements are true for skeletal muscle.

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