Week 1 - Lecture 3 - Clinical Models Flashcards
what is cerebral atrophy
reduction in size of the cells in the cerebrum of the brain
- progressive reduction in the size of the brain
- reduction in brain tissue itself
Cerebral atrophy cont
neutrons are the functional cells in brain tissue
they conduct nerve impulses
- within the brain
- to other areas of the body
loss of neuronal function due to atrophy leads to neurological disease
- as we age, cerebral atrophy progresses
- clinical symptoms start to appear after a certain degree of atrophy
pathophysiology of cerebral atrophy
neurons are connected and communicate
- destruction of neutrons and loss of neurotransmitter in one part of the brain may lead to atrophy in another part of the brain
some injury types
- reduced perfusion : increased risk of deficit injury (oxygen and nutrient delivery impacted)
-intoxication : due to ischemia, metabolites accumulate
as neutrons decrease in size
- physical relationship with other neurons changes
- communication between neurones impaired due to increasing distance
neutrons are not able to replicate
neural cell death : permanent loss of cells and function
clinical manifestations of cerebral atrophy
focal : localised to a particular region
global : affecting entire brain
neurons in each area responsible for specific functions of the brain
as atrophy progresses, the associated function becomes altered
frontal lobe/temporal lobe : cognitive impairment
hippocampus/ cerebral cortex : alzheimer’s
basal ganglia : movement disorders
wide range of clinical manifestations
- depends on the location of atrophy and the extent
Diagnosis - cerebral atrophy
brain atrophy is a pathological finding
- identify possible etiology
- initiate possible treatment
medical history : signs, symptoms, onset, duration
- identifying onset is difficult (eg. self assessment of cognitive decline)
- insidious and subtle development of signs
- often signs first observed by others
- early identification of loss and function, better prognosis
neurological examination
imaging studies
Cerebral atrophy treatment
atrophied and damage neurons recovery is limited
- prevention is the best approach
- interruption process will stop or slow the course of disease
supportive care to maintain optimal functioning of the individual (physical, speech, occupational therapy)
pharmacologic treatment : to improve neurologic signal transmission
Cardiac hypertrophy
myocytes do not continually divide and replace themselves
- after 4 weeks of life : growth is only by hypertrophy
– you have the same number of functional cells (minus loss of injured/dead cells)
hypertrophy : increased cell size
cardiac hypertrophy : increased cardiac mass
Cardiac hypertrophy cont’
can be physiological or pathological
- physiological cardiac hypertrophy results from excessive exercise
pathophysiology cardiac hypertrophy
primary cardiac hypertrophy (hypertrophic cardiomyopathy)
idiopathic
inherited non-sex linked genetic trait
secondary cardiac hypertrophy (hypertrophic cardiomyopathy)
-due to an underlying condition increasing ventricular workload
increase in ventricular muscle mass results from an increase in myocardial cell size
can occur in both, right and left ventricle
cardiac hypertrophy pathophysiology cont’
ventricle walls become thickened and stiff due to increased cell size
-muscle is less effective at contracting despite the increased size
- result in lack of compliance (stiffness)
adequate filling is not possible
-cardiac output decreases
stiffness +small chamber size = cardiac failure
-clinical signs and symptoms develop slowly
cardiac hypertrophy : clinical manifestations
variable clinical expression
- mild to severe (some do not have symptoms)
left ventricle is the main pump
- decreased circulatory output
- back flow to left atrium
-backflow to pulmonary circulation
- heart own perfusion suffers and impacted, reducing oxygen and nutrient delivery
impaired cardiac function SOB syncope (fainting) irregular heart rate -myocutes enlarge, physical relationship of conducting cells altered -neurologic signalling disrupted
diagnosis for cardiac hypertrophy
family history of the condition
- genetic testing can aid preclinical diagnosis of primary cardiac hypertrophy
secondary cardiac hypertrophy
- identification of primary pathology
- treatment/management of primary pathology
routine screening
- hypertension
- reduced exercise tolerance
- ventricular arrhythmia
- altered signals in the cells of the ventricles
screening techniques
- EKG : electrical activity of the heart
- two dimensional echocardiogram : Ultrasound measurement of physical dimensions
- exercise stress testing : determine cardiovascular response to exercise
-P/E : heart murmur during cardiac contraction often heart
Cardiac hypertrophy treatment
main target: symptom relief and prevention of sudden cardiac death
- pharmacologic
- drugs that relax the ventricles
- drugs that reduce the workload of the heart
beta-adrenergic blockers
–reduce the rate and strength of muscle contraction by binding to and inhibiting norepinephrine and epinephrine receptors - surgery
- to reduce left ventricular mass
- repair heart valves
- complications associated - alcohol ablation of the interventricular septum : necrosis by injecting alcohol into small arteries, new therapy, not enough evidence to understand long term effects
- non-pharmacologic : activity restriction to minimise sudden cardiac death
What is acromegaly
condition of cellular hyperplasia (increase in cell numbers)
Most common clinical manifestation :
- abnormal growth in hands and feet
- megaly : enlargement
- -acro : extremities
pathophysiology of acromegaly
leads to excessive growth
-bone, cartilage, soft tissues, organs
occurs after epiphyseal plate closure in the long bones
-acromegaly affects adults
clinical manifestations of acromegaly
objective signs
-increased extremities, fascial eyebrow, jaw, nasal bone, increased spacing of teeth
organ enlargement
- serious health consequences
- diabetes, cardiovascular disease, colon cancer
- hypertrophy changes as well
- cardiac hypertrophy, heart failure
excessive sweating, body odour
-hyperplasia of glands
Voice deepening, snoring
-hyperplasia of vocal cords, sinuses
skin changes
altered reproduction function
Clinical manifestations of acromegaly cont’
if pituitary adenoma involved
- physical pressure on surrounding structures as adenoma increases in size
- -pressure on brain tissue
- —headaches, impaired vision
- -pressure on pituitary itself
- —altered production of pituitary hormones
List of pituitary hormones
anterior pituitary hormones
- growth hormone
- thyroid stimulating hormone (TSH) or thyrotropin
- adrenocorticotropic hormone (ACTH)
- Follicle-stimulating hormone (PSH)
- Luteinising hormone (LH)
- Prolactin (PRL)
Posterior pituitary hormones
-made by hypothalamus, stored in PP
Oxytocin
Antidiuretic Hormone (ADH)
Diagnosis for acromegaly
1st step : biochemical laboratory analysis
- elevated blood level of pituitary growth hormone (variations in secretions throughout the day, not reliable)
- elevated blood level of IGF-1 (level is more stable, reliable)
- Glucose tolerant test (glucose ingestion suppresses pituitary growth hormone level, elevated level indicated acromegaly
2nd step : establish whether pituitary adenoma is cause
-imaging studies (CT, MRI)
Treatment for acromegaly
treatment is to reverse or reduce the effects of acromegaly
- if identified early, chronic effects can be halted
1. pharmacologic - 1, drugs to reduce growth hormone section
- –1. pituitary growth hormone inhibitors
- –2. dopamine agonist (pituitary level, reduce growth hormone secretion)
- –3. Somatostatin analogs (pituitary level)
- 2, drugs to reduce the size of the pituitary adenoma
2. nonpharmacologic: radiation therapy to promote cell death in growth hormone hyper-secreting cells
3. surgical - removal of tumour (adenoma) causing hyper secretion of growth hormone (transsphenoidal hypophysectomy)
cervical metaplasia and dysplasia
cervical development is a dynamic process
cells of the cervix respond to hormonal changes throughout reproductive life
- adaptive
- metadaptive
cervical metaplasia and dysplasia is the cellular adaptation of the squamous and columnar epithelial cells in the transformation zone of the cervix
Squamous metaplasia in the transformation zone in the cervix
during puberty and at the first pregnancy : the cervix increases in volume in response to hormonal changes
the endocervical epithelium everts onto the ectocervix (portio vaginalis) exposing it to the acidic pH of the vagina. This provides a stimulus for metaplastic change of the columnar epithelium
columnar metaplasia in the transformation zone in the cervix
high oestrogen level
-promote gradual transition of squamous epithelium to columnar epithelium
(the opposite of the squamous metaplasia described on the previous slide)
Metaplasia in the transformation zone in the cervix
metaplastic changes of the cervix are not pathologic
squamous epithelial component of TZ is vulnerable to stressor
-chronic infection
-irritation
-trauma
if stressors are persistent, TZ is the most likely place for cellular dysplasia
- cellular structure changes are apparent in dysplastic cells
cervical dysplasia considered to be a precancerous condition
- if identified and treated early : damaged cells can be removed or the stress prevented
if left untreated
- may recover spontaneously
- may progress into malignancy or cancer
Clinical manifestations of cervical dysplasia and metaplasia
- no signs or symptoms (asymptomatic)
- importance of routine screening (secondary prevention)
risk factors
- early onset sexual activity
- multiple partners (>3)
- exposure to human papilloma virus (HPV) - not all strains of the virus
- smoking
Diagnosis for cervical metaplasia and dysplasia
history and physical examination
screening tests
- pap-smear
- microscopic examination of transformation zone cells
- HPV screening
Diagnostic tests
- based on the result of cellular screening tests
- colposcopy : acre tic acid solution applied to cervix, identifies dysplastic area by colour changes
- punch biopsy of whitened areas
- further biopsy of endocervical tissue for microscopic examination
Cervical metaplasia and dysplasia treatment
risk reduction : eliminate/ minimise risk factors
- gardasil - three dose vaccine protects against HPV 16 & 18
-prevent 71% of cervical cancer worldwide
-recommending in early age women prior to sexual activity
Ian Fraser
elimination of damaged (dysplastic) cells
cryosurgery : form of cold therapy
- liquid nitrogen is applied to dysplastic cells on the ectocervix
-destroy dysplastic cells
Surgical excision : cone biopsy
- cone shaped area removal with scalpel
- large loop electrosurgical excision procedure (LEEP) with wire heated by electric current
cervical carcinoma - hysterectomy may be indicated
Environmental toxins and cardiovascular disease : pathophysiology
exposure to environmental chemicals
- causes physical cell injury
- examples of environmental toxins : CO, nitrates, SO2, ozone, lead, cigarette smoke
Airborne particulate matter
-interact with inflammatory cells causing oxidative damage and inflammation
Toxic injury to cells and tissues
evidence is strong
- air pollution and smoking are known risk factors for cardiovascular disease
Environmental toxins and cardiovascular disease : clinical manifestations
diseases associated with exposure to cigarette smoke
- aortic aneurysm
- acute myeloid leukaemia
- cataract
- cancer (many types)
- pneumonia
- chronic lung disease
- coronary heart disease
- stroke
- reproductive effects
- sudden infant death syndrome
Environmental toxins and cardiovascular disease : diagnosis
smoking is causative and additive factor in cardiovascular disease
history and P/E
- reduced exercise tolerance (impaired ability of hear to meet demand)
- difficulty breathing
- blood clot (pale and cold extremities)
- hypertension
- increased heart rate
- reduced cardiac output
laboratory studies
- may find markers of cardiovascular disease
- hyperlipidemia (increased LDL concentration, bad cholesterol)
environmental toxins and cardiovascular disease : treatment
smoking cessation
pharmacologic treatment
