Histology, Bladder


Article Author:
Srinivasa Rao Bolla


Article Editor:
Raghu Jetti


Editors In Chief:
Stephen Leslie
Karim Hamawy


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Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
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Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
4/11/2019 12:57:07 AM

Introduction

The urine formed by the nephrons of the kidneys is transported to the urinary bladder for storage before it gets expelled through the urethra. The urinary bladder is a sac that serves as a reservoir of the urine; it is located in the pelvis behind the pubic bones and extends into the abdomen when filled with urine. The bladder divides into an upper part above the ureteric orifices, the body or dome and a base that includes the trigone and neck of the bladder. The capacity of the bladder is about 500ml in healthy individuals.[1] As the bladder gets filled, it gets stretched, and afferent signals lead to the efferent signals resulting in contraction of the bladder musculature and relaxation of the urethral sphincter, respectively. Along with the stretch signals, various psychological factors like stress, sense of acceptable surrounding, and emotional status play a key role in micturition to take place at an appropriate place and time[2]. In this section, we describe the detailed microscopic structure of the urinary bladder wall. 

Structure

The microscopic structure of the urinary bladder wall organizes into the following layers from inside out. 

  • Lining epithelium
  • Lamina propria
  • Muscularis propria
  • Serosa

Lining epithelium: The urinary bladder lining is a specialized stratified epithelium, the urothelium (transitional epithelium). Urothelium is exclusively seen only in urinary structures such as the ureter, urinary bladder, and proximal urethra. Urothelium in the relaxed urinary bladder is five to seven cells thick and has three layers[3][4][3]:

  • Apical layer - The innermost layer in contact with urine, serve as a barrier between the underlying tissue and, made of a single layer of umbrella-shaped cells that are frequently binucleated. These apical umbrella cells of the urothelium form an impermeable barrier by tight junctions between the cells and are covered by a layer of plaque  formed by uroplakin providing an additional barrier function
  • Intermediate layer - Formed from two to three layers of polygonal cells.
  • Basal layer - Is made of two to three layers of small cuboidal cells. 

In a relaxed urinary bladder, urothelium is five to seven layers thick. When the urinary bladder fills with urine, it greatly distends stretching the bladder wall. In the distended bladder, the urothelium becomes two to three layers without any structural damage. Due to this transitional ability of the urothelium, it is also known as transitional epithelium.

Lamina Propria: Lamina propria is the suburothelial layer separating the urothelium and underlying muscularis propria(Detrusor muscle). It is separated from the overlying urothelium by a basement membrane. Its composition is an extracellular matrix with elastic fibers, capillaries, lymphatics, immune cells, afferent and efferent nerve endings, fibroblasts, myofibroblasts, adipocytes, interstitial cells of Cajal or telocytes, and indistinct smooth muscle layer, and the muscularis mucosae. 

The interstitial cells of Cajal are in the lamina propria between urothelium and detrusor muscle; they form the syncytium with the smooth muscle cells and nerve endings. The interstitial cells of Cajal are said to function as pacemaker cells in the gut, urethra, and prostate. In the bladder, they might be acting as nerve signal transducers to smooth muscles.[5]

Muscularis propria: This layer is made up of the smooth muscle coat with the interstitial connective tissue of the urinary bladder wall, known as the detrusor muscle. It consists of three layers, inner and outer longitudinal and middle circular layer. This muscle is well defined around the neck of the urinary bladder as inner circular and outer longitudinal layers. In the rest of the bladder wall, they run randomly with no orientation. The body of the bladder has a higher smooth muscle content compared with the trigone, reflecting a well-developed network of myofibroblasts of lamina propria and muscularis mucosae.[6]

Serosa: The serosa is connective tissue covered with the mesothelial lining partially on the surfaces of the urinary bladder that has a peritoneal covering. It also contains blood vessels of various sizes.

Function

The urothelial lining of the urinary bladder with its ability to transform from 5 to 7 cell layers thickness in a relaxed state to 2 or 3 cell layers in a distended bladder provides a functional modification of the epithelium without any damage. In the superficial layer,  umbrella-shaped cells are connected by tight junctions and covered by uroplakin, thus making it a barrier preventing injury to the tissue below.[7] Lamina propria along with the urothelium is a sensory region regulating the micturition reflex. The extracellular matrix with the nerve endings, myofibroblasts might have a role in reflexes of the bladder.[8] Lamina propria acts as a "functional center" of the bladder because of the presence of many specialized cells. It serves as a capacitance layer of the bladder that determines its compliance.[9] The detrusor muscle of the muscularis propria is under the autonomic nervous control. Sympathetic stimulation relaxes the detrusor and stimulates the urethral sphincter to allow filling of urine and parasympathetic contracts the detrusor and relaxes the urethral sphincter to allow the micturition.

Tissue Preparation

Tissue biopsy for histopathological examination is taken by cystoscopy or from radical cystectomy samples. Percutaneous bladder biopsy under image guidance is an option when cystoscopy is not possible.[10] Formalin-fixed tissue embedded in paraffin wax or frozen sections is used for routine hematoxylin and eosin histopathology of the urinary bladder. 

Histochemistry and Cytochemistry

The umbrella-shaped top layer of cells are CK20+, and the basal cells are CD44+. In carcinoma in situ, all cells are CK20+, p53+ and show greater Ki-67 proliferation index.[11]

Microscopy Light

Under the light microscope, in the histological section of the bladder wall, the urothelium, lamina propria, muscularis propria, and serosa are seen. Urothelium has a superficial dome-shaped umbrella cell layer whose shape becomes flat in a distended bladder. The cells of this layer are often multinucleated. Below the superficial umbrella cell layers are multi-cell layered intermediate and a single basal cell layer contacting the basement membrane. The cells of the intermediate layer are uninucleated; the number of layers in the intermediate layer depends on the stage of distension of the urinary bladder.[7] The basal layer has mononucleated cells, cuboidal in shape and shows the capability of mitosis. Even though the rate of turnover is not rapid, it demonstrates great regenerative capacity. The lamina propria is a suburothelial layer' the contents described in the Structure section above.

Microscopy Electron

The cell membrane superficial cells shows an unusual feature called plaques or asymmetrical unit membrane. These are more rigid and thicker than other areas of the cell membrane. Actin filaments extend from the inner surface of the plaques to the cytoplasm. In the undistended bladder, the superficial cells appear to fold inwards, because of this folding plaques are seen as fusiform vesicles. When the bladder distends these vesicles unfold and become part of the surface.

Pathophysiology

Overactive bladder the urinary urgency could be due to neurogenic, myogenic or idiopathic reasons. The mucosal signaling that involves autonomic nerves and the cells of the mucosa are likely to be involved in conditions like overactive bladder, bladder pain syndrome[2]

Clinical Significance

Cystoscopy is used to examine the urinary bladder mucosa for pathology and to collect biopsy samples. Bladder tumors are graded based on their depth of invasion into the bladder wall. Islands or nests of the urothelium (von Brunn's nests) get separated from the surface found in lamina propria. These nests may undergo degeneration to form cysts which lead to cystitis cystica.


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Histology, Bladder - Questions

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In the histopathology report of a patient who underwent a biopsy, the pathologist stated the presence of Von Brunn's nest. These cells are part of what organ system?



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How many cell layers thick is the urothelial layer of the bladder?



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Which of the following tissue types is found as the lining epithelium of the urinary bladder?



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The apical umbrella cells of the urothelium are impermeable by the covering of which of the following?



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Which of the following accurately characterizes the smooth muscle coat of the urinary bladder that is known as the detrusor muscle?



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Histology, Bladder - References

References

Sellers D,Chess-Williams R,Michel MC, Modulation of lower urinary tract smooth muscle contraction and relaxation by the urothelium. Naunyn-Schmiedeberg's archives of pharmacology. 2018 Jul;     [PubMed]
Chai TC,Russo A,Yu S,Lu M, Mucosal signaling in the bladder. Autonomic neuroscience : basic     [PubMed]
Abelson B,Sun D,Que L,Nebel RA,Baker D,Popiel P,Amundsen CL,Chai T,Close C,DiSanto M,Fraser MO,Kielb SJ,Kuchel G,Mueller ER,Palmer MH,Parker-Autry C,Wolfe AJ,Damaser MS, Sex differences in lower urinary tract biology and physiology. Biology of sex differences. 2018 Oct 22;     [PubMed]
Walz T,Häner M,Wu XR,Henn C,Engel A,Sun TT,Aebi U, Towards the molecular architecture of the asymmetric unit membrane of the mammalian urinary bladder epithelium: a closed     [PubMed]
Drumm BT,Koh SD,Andersson KE,Ward SM, Calcium signalling in Cajal-like interstitial cells of the lower urinary tract. Nature reviews. Urology. 2014 Oct;     [PubMed]
Khandelwal P,Abraham SN,Apodaca G, Cell biology and physiology of the uroepithelium. American journal of physiology. Renal physiology. 2009 Dec;     [PubMed]
Butros SR,McCarthy CJ,Karaosmanoğlu AD,Shenoy-Bhangle AS,Arellano RS, Feasibility and effectiveness of image-guided percutaneous biopsy of the urinary bladder. Abdominal imaging. 2015 Aug;     [PubMed]
Vannucchi MG,Traini C,Guasti D,Del Popolo G,Faussone-Pellegrini MS, Telocytes subtypes in human urinary bladder. Journal of cellular and molecular medicine. 2014 Oct;     [PubMed]
Sánchez Freire V,Burkhard FC,Schmitz A,Kessler TM,Monastyrskaya K, Structural differences between the bladder dome and trigone revealed by mRNA expression analysis of cold-cut biopsies. BJU international. 2011 Jul;     [PubMed]
Wang G,McKenney JK, Urinary Bladder Pathology: World Health Organization (WHO) Classification and American Joint Committee on Cancer (AJCC) Staging Update. Archives of pathology     [PubMed]
Andersson KE,McCloskey KD, Lamina propria: the functional center of the bladder? Neurourology and urodynamics. 2014 Jan;     [PubMed]

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