Cell adaptations

Cell adaptations

1. Introduction

   • Normal cell (homeostasis)
     • Stress, increased demand
       • Adaptation
         • Inability to adapt
     • Injurous stimulus
       • Cell injury -> cell death
   • Cell adaptation
     • Many cell adaptations involve changes in cell growth, size or even differentiation
     • Adaptations are a physiological event but also occur in response to pathological/abnormal stimuli

2. Adaptive mechanisms

   • Hyperplasia
     • Increase in the number of cells in a tissue resulting in an increase in the size of the organ
     • Physiological (normal)
       • Hormonal
         • Breast tissue at puberty/pregnancy
         • Uterine smooth muscle during pregnancy
       • Compensatory
         • Following partial hepatectomy
         • Chronic hypoxia (increase in RBCs)
     • Pathological
       • Hormonal
         • Unopposed effect of oestrogens on endometrium
       • Despite pathological hyperplasia being reversible it may be a risk for developing malignancy
       • Wound healing
         • Kelloid formation
   • Hypertrophy
     • Physiological
       • Hormonal
         • Uterus in pregnancy
       • Compensatory
         • Increase in skeletal muscle in body builders
     • Increase in the size of the cells in response to an increased demand
       • Not accompanied by cell division, although hypertrophy and hyperplasia may co-exist
     • Pathological
       • Increase in the size of cardiac muscle in response to obstruction (valvular disease) or ioncreased resistance (hypertension)
         • Hypertrophy of the cardiac muscle is accompanied by a change in gene expression - e.g. fetal contractile genes re-activated
           • aloha-myosin heavy chain (MHC) expressed in normal adults and beta-MHC in fetal heart - this fetal version has a lower level of ATPase activity
             • ... It also contracts more slowly. The switch from alpha to beta form is associated with hypertrophy
       • Hypertrophy of bladder muscle due to prostate disease
   • Atrophy
     • Pathological
       • Decreased workload
         • Disuse atrophy (e.g. skeletal muscle wasting following a fracture and immobilisation)
       • Loss of innervation
         • Denervation atrophy
       • Diminished blood supply
         • Brain atrophies with age as supplying blood vessels become narrower
     • Partial or complete wasting of tissue due to pathological process
   • Hypoplasia
     • Failure to achieve normal size of organ due to developmental abnormality (e.g. hypoplastic left heart)
   • Metaplasia
     • A reversible event in which one adult, fully differentiated tissue type is replaced by a different fully differentiated type
       • Which is better suited to the new environmental conditions
     • Physiological
       • Change in endocervical epithelium from glandular to squamous (squamous metaplasia)
         • This area is called the transformation zone
           • From glandular tissue (vagina) to the cerical tissue (stratified squamous)
     • Pathological (adaptation to stimulus)
       • Squamous metaplasia in respiratory tract due to chronic irritation
       • Squamous metaplasia of salivary gland ducts/bile ducts (due to obstruction)
       • Squamous metaplasia of urinary bladder due to chronic infection
       • Squamous to columnar metaplasia in oesophagus (Barrett's oesophagus) - - due to chronic acid reflux
     • Although regarded as an adaptive response, metaplastic tissue is 'unstable', and areas of metaplasia are frequent sites for neoplastic development
       • Cervical cancer
       • Barrett's oesophagus
       • Lung carcinoma on the back of squamous metaplasia

3. Dysplasia and anaplasia

   • Dysplasia is disordered differentiation (classic malignant appearance)
   • Anaplasia is a lack of differentiation
   • Characterised by several features
     • Pleomorphism
       • Variation in size and shape
     • Abnormal nuclear morphology
       • Nuclei contain abundant DNA and are dark staining - hyperchromatic
     • Mitoses
       • Reflecting increased proliferation
     • Loss of polarity
       • Orientation of cells is disturbed

4. What determines a cell's response?

   • Major factor is the cell type
   • Three populations identified
     • Labile cells
       • Continually dividing cells
         • Squamous epithelium (skin, mouth and other mucous membrabes)
         • Glandular epithelium of the intestines
         • Haemopoietic cells
     • Stable cells
       • Normal rate of growth/turnover is very slow - but can be accelerated in response to stimuli
         • e.g. liver, renal tubular epithelium and endocrine glands
     • Permanent cells
       • Cells unable to divide
         • e.g. neurones, heart and skeletal muscle
   • Susceptability to cell injury
     • Depends on...
       • Cell type (active membrane exchange - renal tubular cells; neurones have very little ability to use anaerobic respiration)
       • Metabolic state of the cell (depleted reserves of glycogen - liver damaged by alcohol/drugs)
     • Susceptability to hypoxia (low O2)
       • High
         • Neurones (3-5mins)
       • Medium
         • Myocardium, hepatocytes, renal tubules (30mins - 2hrs)
       • Low
         • Fibroblasts, skeletal muscle (many hours)