Cells Flashcards
Which 6 hormones are secreted from anterior pituitary?
FLAT GP
FSH, LH, ACTH, TSH, GH, PTH
Which 2 hormones are secreted from the posterior pituitary?
ADH, oxytocin
Where is the neuroendocrine system?
Glands with predominant endocrine function
Collections of tissues within other specialised organs
Dispersed as single cells i.e. the diffuse neuroendocrine system derived from neural crest cells
Co-production of amine hormone/transmitters, peptide hormone/transmitters
Where are Neuroendocrine cells present as single dispersed cells?
Enteric
Pulmonary
Which cells of the thyroid secrete calcitonin?
C cells
Describe the location of the Neuroendocrine system
Pineal gland Hypothalamus Pituitary gland Thyroid gland Parathyroid glands Adrenal glands Pancreas Gonads
What do Neuroendocrine cells look like?
Lots of vesicles
Nucleus away from the site, prominent nucleolus
Close proximity to neurons
Abundant granular cytoplasm
Why are Neuroendocrine cells particularly important in health and disease?
Can be location of cancers
What are the hallmarks of neuroendocrine cells?
Amine precursor uptake and decarboxylation
Possession of cytoplasmic neurosecretory vesicles
What are the cellular layers of the adrenal gland?
Capsule Zona glomerulosa - secretes aldosterone Zona fasiculata - secretes cortisol Zona reticularis - androgens Adrenal medulla - Neuroendocrine cells, paraganglia
What is pheochromocytoma?
Neuroendocrine tumour of medulla of adrenal gland
Secretes high amounts of catecholamines
Present with sympathetic symptoms
Give examples of Neuroendocrine cells
C cells in thyroid
Juxtaglomerular apparatus
Paraganglia - aortic and carotid bodies
What are carcinoid tumours?
Neuroendocrine tumour
Carcinoid syndrome - collection of symptoms, usually when it has spread to the liver
What controls levels of prolactin?
Dopamine
What is special about the hypothalamic blood supply?
Hypophyseal portal system
Connects it to anterior pituitary
Allows fast communication
What are the roles of Neuroendocrine cells in the enteric system?
Regulate intestinal movements and the release of digestive enzymes
What are the roles of Neuroendocrine cells in the respiratory system?
Developmental stages of the respiratory organs
Regulate respiratory function
Important in lung damage
Describe the Neuroendocrine involvement in hypoglycaemia
Low glucose levels cause signal to hypothalamus, adrenal medulla and pancreas
Hypothalamus leads to increased cortisol to rebuild glucose stores
Adrenal medulla secretes adrenaline which releases stored glucose and decreases utilisation
Pancreas secretes glucagon to promote glucose release from stores
What 5 Factors affecting cellular aging and degeneration?
Genetics Diet Social Age related disease Cellular alterations
What 6 factors can cause cell injury?
Deceased ATP Mitochondrial damage Entry of Ca ROS Membrane damage Protein misfolding DNA damage
What are potential consequences of cellular ageing?
Reduced capacity to function
Reduced capacity to respond to injury
Cell Death
What causes cellular aging?
Exposure to harmful exogenous influences
Cellular and Molecular damage including genetic abnormalities Progressive declinein cellular function and viability
What is replicative senescence?
Decreased cellular replication due to decreasing telomere length
What Changes contribute to cellular aging?
Replicative senescence
Accumulation of metabolic and genetic changes
Reactive Oxygen Species Injure cells
How do Reactive Oxygen Species Injure cells?
Membrane lipid peroxidation
Interaction with proteins
DNA damage
What is the pattern of clinical features of Alzheimer’s disease?
Impaired higher functioning, change in mood and behaviour
Disorientation, memory loss and aphasia
Profound disability and immobility
Death
What pathological changes cause Alzheimer’s?
build up of beta amyloid (Aβ) from amyloid precursor protein (APP)
Alpha secretase precludes AB formation as it cleaves through middle
Beta and gamma secretase lead to AB formation which form plaques
This causes kinase activation which phosphorylates tau
Micro tubules disassemble and form tangles
What is the link between Down’s syndrome and Alzheimers?
Increased copies of the gene for APP on chromosome 21
What macro pathology will be seen in Alzheimer’s?
Cortical atrophy especially in the frontal, temporal and parietal areas
Hydrocephalus ex vacuo - ventricles appear enlarged
Describe the micro pathology of Alzheimer’s
Extracellular plaques: Neuritic processes around amyloid core
Diffuse plaques without neuritic response
Intracellular neurofibrillary tangles: Paired helical proteins that
displace or surround the nucleus of the neurone
Associated neuronal loss and glial reaction
Describe the pathology of ALS
Various genetic abnormalities: SOD1
Reduced capacity to detoxify cells, misfolded proteins cause ER stress
cause cell injury
This results in loss of UMN in cerebralcortex and LMN in spinal cord and brainstem - particularly corticospinal tracts
What is Friedreichs Ataxia?
Autosomal recessive condition, GAA trinucleotide repeat
Spinocerebellar degeneration
Affects parts of the Spinal cord, brainstem and cerebellum leading to loss of axons and gliosis
What is Invasion?
Ability of cells to break through normal barriers e.g. basement membrane and then spread into surrounding tissue
In lymphatic/vascular channels
Path of least resistance e.g. perineural
Characteristic of malignant cells
How do cells invade and spread?
Malignant cells - less adherent
Cadherins: calcium dependent glycoproteins in membrane interact between cells and within cell with the actin cytoskeleton through catenins, maintaining cell polarity. Reduced expression and alterations in interactions in cancer cells, allowing cells to move apart
Integrins: cell surface glycoproteins with 2 subunits, receptors for different components of basement membrane eg. fibronectin
Reduced expression of integrins in malignant cells modifies the contact between the cell and stroma
Altered synthesis of enzymes that breakdown basement membrane and stroma: Three families of matrix metalloproteinases (MMPs) 1.collagenases (degrade collagen I-III))
2. gelatinases (collagen IV and gelatin)
3. stromelysins (collagen IV and proteoglycans)
What are MMPs (matrix metalloproteinases) counteracted by?
Tissue Inhibitors of Metalloproteinases (TIMPS)
What is Metastasis?
Ability of malignant cells to invade lymphatics, blood vessels and cavities and spread to distant sites
Cells must be able to invade out of channels and grow at distant site
Not all circulating cancer cells will settle at a distant site and be able to grow
Describe the process of metastasis
In situ cancer Invades tissue border via basement membrane and ECF Spreads in lymphatics Intravasion of circulatory system Survival and transport Arrest extravasion Solitary dormant cells, occult micrometastases Progressive colonisation, angiogenesis
Why don’t all malignant cells metastasise?
Cells may invade and circulate May get to distant site but environment not appropriate for growth Incorrect receptors Metabolic factors Failure of angiogenesis
What is Angiogenesis? And how is it relevant to Cancer?
Formation of small new vessels needed to maintain growth of cells
Due to various growth factors produced by cancer cells
Can aid invasion – more vessels with thin walls
Aids growth of metastasis
What factors are involved in angiogenesis?
Vascular Endothelial Growth Factor (VEGF)
Basic Fibroblast Growth Factor (bFGF)
Angiopoietins: Ang 1: stabilises small vessels, Ang 2: remodelling
Anti-angiogenetic factors: Thrombospondin, angiostatin, endostatin,
vasostatin
What are options for tumours requiring vessels?
Tumour-induced stimulation of angiogenesis: angiogenic switch
Vasculogenic mimicry: tumour cells can express endothelial antigens, reversion to an embryonic phenotype
Vessel co-option: invasion around vessels with death of lining endothelial cells leads to tumour cells lining vascular spaces
What are the routes of Metastasis?
Lymphatics: Spread to local and distant lymph nodes, Frequent route of spread of carcinomas, Can involve lymphatics of lung
Blood vessels: Spread through capillaries and veins to various organs, Common sites are lung, liver,bone and brain
Coelomic spaces
Which cancers can spread vascularly to the lung?
Sarcomas eg. Osteosarcoma
Carcinomas eg. breast, stomach, large intestine
Kidney (cannonball)
Testis eg. malignant teratoma
Which cancers can spread vascularly to the liver?
Common site for carcinomas of large intestine (portal vein)
Bronchial carcinoma
Breast Carcinoma
Which cancers can spread vascularly to the bone?
Can cause destruction of bone: Bronchial carcinoma, Breast carcinoma, Thyroid carcinoma, Renal carcinoma
Cause production of dense bone (osteosclerosis): Prostate
Which cancers can spread vascularly to the brain?
Bronchial carcinoma
Breast carcinoma
Testicular carcinoma
Malignant melanoma
Which cancers can follow a Transcoelomic Spread?
Ovary
Stomach
Breast
Lung
What factors determine the effect of a tumour?
site of tumour extent of local spread site of metastasis extent of metastatic spread functional effects paraneoplastic effects
What are Paraneoplastic Effects?
Not local Not metastases Not indigenous hormone effect Examples: Dematomyositis Humoral factors excreted by tumour cells or an immune response against the tumour which cause symptoms
What are Local Effects of Neoplasia?
Benign: Cause compression, pressure atrophy, altered function eg. pituitary, partial or complete obstruction, Ulceration of surface mucosa
Space occupying lesion – brain
Malignant: Tend to destroy surrounding tissue, partial or complete obstruction, constriction, Ulceration, Infiltration around and into nerves,
blood vessels, lymphatics, Space occupying lesion - brain
What are systemic effects of neoplasia?
Haematological
Anaemia: ulceration (benign and malignant), infiltration of bone marrow (leukaemia, metastasis), haemolysis
Low white cell and platelets: infiltration of bone marrow, treatment
Thrombosis: carcinoma of pancreas
Endocrine
Excessive secretion of hormones: benign (and malignant) neoplasms of endocrine glands e.g.parathyroid hormone, corticosteroids
Ectopic hormone secretion: ACTH by small cell carcinoma of
bronchus
Skin
Pigmentation: Many Carcinomas
Pruritis (itching): Jaundice, Hodgkin Lymphoma, MPD
Herpes zoster: Lymphoma
Dermatomyositis: Bronchial carcinoma
Neuromuscular
Problems with balance
Sensory/sensorimotor neuropathies
Myopathy and myasthenia
Progressive multifocal leucoencephalopathy
Other
Cachexia - wasting
Malaise – severe fatigue
Pyrexia – high temperature
Why do cancers kill?
Local effect e.g. brain, perforation, haemorrhage
Replacement of essential body organs
What are signs of Meningeal irritation?
Headache Stiff neck Aversion to light (photophobia) Confusion, sleepiness, fits Fever Under 50% have all, but 95% have at least 2
What are signs of sepsis relating to meningitis?
Fever
Cold peripheries
Rash: Non-blanching, Purpuric, Haemorrhagic, Not painful/ itchy
How do you manage meningitis and septicaemia?
Medical emergency: do NOT delay treatment while you investigate
Sepsis six: High flow oxygen, blood cultures, broad spectrum antibiotics, IV fluid challenges, serum lactate and haemoglobin, hourly urine output
Investigations
Microbiological investigations
What organisms commonly cause meningitis?
Neisseria meningitidis (meningococcus): 20% of meningitis, Vaccine exists against multiple serotypes
Streptococcus pneumoniae: 20% of meningitis, common in elderly
Haemophilus influenzae: Historically important, Virtually eliminated by childhood Hib vaccine
Group B Streptococcus (GBS): Increasingly common in infants, Rare over age 12 months
Listeria monocytogenes: Uncommon, risk in pregnancy, Elderly (>55 years), Immunocompromised, Linked with consumption of unpasteurised dairy products and Cook-chill foods, Classically causes a meningo-encephalitis
50% cases viral: Many are mild and not reported, Enterovirus, Mumps, Herpes simplex
What drug management would be used in meningitis?
Follow local guidelines
Ceftriaxone: Covers meningococci, pneumococci and Haemophilus Add amoxicillin to cover Listeria in risk groups
Add aciclovir if encephalitis clinically suspected
What should be done about notifying about meningitis?
Statutory: NOIDS regulations, GMC requirement to comply
Protection of public health
Protection of healthcare workers
Epidemiological monitoring: vaccine efficacy, cost-effectiveness
What are prognoses like for meningitis?
Bacterial: virtually 100% mortality prior to antibiotics, Now approximately 10% mortality, Higher for S. pneumoniae, Neurological sequelae common, especially H. influenzae and S.pneumoniae, Seizures, Developmental delay, Hearing loss
What preventions exist for meningitis?
Vaccines exist against Meningococcus A,C,W, Y and now B, Pneumococcus, Hib
Some causes of viral meningitis
Chemoprophylaxis (kissing contacts), Meningococcus only
Describe clinical features of encephalitis
Symptoms and signs of cerebral dysfunction
Meningo-encephalitis
Non-specific symptoms: Headache, Nausea and vomiting, Fever, Behavioural change, Seizures, Altered consciousness
What are common organisms causing encephalitis?
Predominantly viral: Herpes simplex most common
Influenza, Mumps, Measles (SSPE), Polio, Rabies
What are management options for encephalitis?
Supportive care
Specific antiviral treatment for herpes simplex
Better outcome if given early
Treat and then confirm diagnosis
What is the prognosis for encephalitis?
70% mortality if untreated
High rate of sequelae, especially memory loss
What are clinical features of cerebral abscess?
Rare in the antibiotic era Present with headache, fever and focal neurological signs Usually polymicrobial Oral bacteria, including Streptococci Diagnosed by scan plus biopsy Main differential is tumour
What biochemistry should be done on a CSF sample to look for infection?
1 sample to biochemistry
2 (1st and 3rd) to microbiology
Biochem: protein, glucose (send a blood glucose too), (xanthochromia) Cell count and gram stain
If the cause of meningitis is bacterial, what will show up in CSF tests?
High white cell count
Neutrophils predominant
High protein
Low glucose
If the cause of meningitis is viral, what will the CSF contain?
Slightly high white cell count
Lymphocytes predominant
Slightly high protein
Normal glucose
What cultures should be sent for a suspected meningitis case?
CSF: positive less likely if antibiotics before sample (always send CSF sample unless specific contraindication)
Blood culture: easier to obtain before antibiotics, more likely to be positive
Throat swab: helpful to look for meningococci
Viruses will not be cultured, but may be detected in blood, CSF or throat swabs
Different swabs for viral and bacterial throat samples as charcoal in standard bacterial swabs inhibits the PCR required for viral detection
What are Contraindications to lumbar puncture for CSF sampling?
Signs of raised intracranial pressure: GCS 2 fall, Focal neurology, Seizures, Bradycardia & hypertension, Papilloedema Coagulation abnormality Superficial infection at LP site Shock/ convulsions until stabilised Extensive/ spreading purpura
What are the 3 mechanisms of hormone release?
Humoral - eg change of Ca in blood stimulates PTH release
Neural - eg adrenal medulla stimulated by SNS
Hormonal - eg hypothalamus secretes releasing hormones to stimulate hormone release from anterior pituitary
