Week 1 Neoplasia
CANCER: CELLULAR REPRODUCTIONS
- Under a normal conditions, cellular reproduction ( i.e cell division or
proliferation )is tightly regulated process
- Cells respond to certain stimuli and growth factors by altering their rate of
reproduction
- Embryogenesis: is a time of rapid proliferation of non specialized (
undifferentiated) cells called stem cells.
- During development cells become specialized in function and structure; some
are more differentiated than others
- The cell cycle refers to the stages of cell goes through during its lifetime,
including cell division
- The more specialized a cell, the less frequently that cell goes through the cell
cycle to divide. Less differentiated cell cycle more frequently.
- Cancer is a condition of unregulated ( uncontrolled) cell production
THE CELL CYCLE
● The stages of a cells life with respect to its reproduction is called the cell cycle
● The cell cycle has four distinct phases:
1. Mitosis ( M phase) is the phase of cell division; continually dividing cells
cycle from one mitosis to the next
2. G is the post mitiotic growth phase where RNA and protein synthesis
and cell growth occurs
3. S phase where DNA synthesis occurs in preparation for cell division
4. G2 is the pre-mitotic phase, also characterized by RNA and protein
synthesis
- Most cells in our body halt their cell cycle in G1 during some point in their
lifespan and enter a phase that is often called G0. this allows cells to
differentiate for specialized functions, these cells enter the cell cycle in
response to growth stimuli
- Highly differentiated cells exit the cell cycle and therefore do not divide
Cellular adaption and transformation
- Cells can adapt to their environment and stimuli in a number of
ways:
1. Atrophy: decrease in cell size
2. Hypertrophy: increase in cell size
3. Hyperplasia: increase in cell number
4. Dysplasia; cells display increased mitosis, are varying sizes and
shapes, and have large nuclei, they are considered
pre-cancerous
5. Neoplasia: cells are divided out of control and have abnormal
cell structure. They are said to have been transformed into
cancerous cells.
Cancer definitions
-
Cancer is the 2nd leading cause of death in canada and the US. and includes almost
all malignant neoplasms
- Neoplasm or tumor: an abnormal mass of cells which grow without response to
normal regulatory controls tend to grow after the stimulus for growth has ceases
- Malignant ( cancerous) tumors are usually consists of less differentiated abnormal
cells which proliferate at a high rate; cells from an irregularly shapes mass cells
invade( spread) surrounding tissue and break away to form new tumors at distant
sites ( i.e metastasize)
- Benign tumors usually consist of more differentiated, relatively normal cells wich
proliferate at a higher than normal rate cause damage to adjacent tissue by
compression; do not spread are usually not life threatening
Malignant neoplasms simply the division of abnormal cells without control and it can
invade the nearby tissues. In addition this cells can spread other parts of the body
through blood and the lumph system.
Malignant cells
- are believed to develop from mutations that occurs during differentiation
Are undiffrentaied (can’t recognize what makes it different) and are much
different from the normal tissue cells surrounding them, especially W.R.T
function, nuclear size and shape
-
Lack contact inhibition, adhesiveness and cohesiveness- invasion and
metastasis
-
Local and systemic effects of tumor
locally , malignant tumors cause death to surrouding tissues in several ways
- Tend to compress blood vessels and outgrow their blood supply
- Iscehmia and tissue necrosis
- Rob normal surrounding cells of nutrients ( nutrient trapping)
- Replace normal tissue
- Loss of function
- Liberate toxins and enzymes that destroty both normal and tumor tissue
- Causes obstruction of passageway
- Cause pain e.g by putting pressure on sensory nerves
Systemic effects
- Anemia
- Weakness and fatigue
- Weight loss ( cachexia)
- Bleeding
- Infections
SPREAD OF MALIGNNAT TUMORS
Malignant tumors spread by producing secondary tumors that are identical to the original
primary tumor
-Tumors spread by three ways:
1. Invasion of neighbouring tissues
2. Metastasis- the spread of cancerous cells through blood and lymph system to other
organs or tissues of the body
3. Seeding - the spread of to a culture vessel for cell culture activities
Invasion
- occurs when tumor cells grow into adjacent tissue. Tumor cells lack adhesive
properties and can secrete enzyme that allow them to break down confining
conecctive tissue
Metastasis
-
Metastasis occurs when tumor cells break free of a tissue and are circulated to
distant tissues in the blood and/ or lymph
- Secondary tumors can be contained by local lymph nodes or lodge in capillary beds
they come across
- The lungs are a common site of metastasis because pulmonary capillaries are often
the first beds encountered by systemic tumor cells the liver is also a common site for
2 dgree tumors
Seeding
- Seeding involves the spreading of tumor cells along membranes or within fluids
other than blood or lymph
- Malignant cells break away and travel with the movement of fluid e.g> ovarian
cancer can spreadthroughout the peritoneal cavity
Development of cancer ( carcinogenesis)
- Carcinogenesis: the process by which normal cell become transformed into
malignant cells; initially involves changes in the DNA ( mutation) most cancers
require multiple changes in DNA caused by several factors
Stages of carcinogensis
1. induction/initation: exposure to carcinogenic agents tha causes the initial
irreversible genetic modification agents may be chemical, physical or biologic
2. Promotion: previously initiated cells are induced into unregulated proliferation by
various promoter chemicals, grwth factors and hormones—tumor development; this
stage is reversible if promoter is removed; may occur after long latency period after
initiation chracterized by dysplasia
3. Progression: tumro cells ( unregulated growth) acquire malignant changes that
promote invasiveness, metastatic properties and autonomous growth; chrctarized
by anaplasia
- Initiators: radiation, components of cigartte smoke, hydrocarbons, certain
dyes, nitrosamines, aflatoxin, asbestos, certain veruses
- Promoters: hormones, nitrate, cigarette smoke, alcohol
Genteic chnages in carcinogenesis-proto-oncogenes
-
There are two main classes of genes responsible for controlling cell growth and replication:
proto-oncogenes and tumor suppressor genes
Proto-oncogenes promotes controlled growth; when genetically altered, proto-oncogenes
become oncogenes which confer unregulated proliferative and invasive properties on the
cells
-
Protein encoded by proto-oncogenes include surface membrane proteins, cytoplasmic
proteins-conveying signals and proteins that bind to DNA and regulate gene transcription
Examples of oncogenes
oncogene
Functions of oncogne protein
Tumor type
HER2
Cell surface recptros
Breast, cancer, ovarian
ras
G protein ( signaling)
Lung, colonic, pancertaic
Myc
Transcription factor
Multiple tumor types
fes
Tyrosine kinase ( singaling)
Leukemia- blood cell cancer
Tumor suppressor genes
-
Tumor supressor genes normally inhibit growth; when genetically altered, control function are lost
leading to unregulated proliferation
Protein encoded by tumor suppressor genes include cell cycle regulators, surface receptors. Cell
adhesion proteins transcirpting factor DNA repair proteins
Research evidence suggests that mainly human neoplasms result from a combination of oncogene
acriavtion and tumor suppressor gene inactivation
Examples of tumor suppressor genes
T.S. game
Functions of T.S. gene protein
Tumor types
P53
Cell cycle regaualtor
Several
Retinoblastoma ( RB)
Cell cycle regulator
Retinoblastoma, small cell
lung cancer , sarcoma , breast
and ovarian
brca1
DNA repair
Breast, ovrain
Ras an example of an oncogene
-
-
proliferation of many cell types is regulated by growth factors or mitogens secreted locally into the
tissue. Examples include: insulin like growth factor, vascular endothelial growth factor, fibroblast
growth factors, and transforming growth factor.
These growth factors exerts their effects by binding to membrane receptors and activation and
intracellular signaling cascade that ultimately increases the production of proteins responsible for
cell type progression
-
Ras is involved in growth factor signaling by activation the mitogen activated signaling cascade
which increases proliferation
When the gene that codes for Ras is mutated, the Ras protein can continuously activate cellular
proliferation, even in the absence of growth factors. This mutation is a common finding in lung,
colon and pancreatic cancers
P53; AN example of a tumor suppressor gene
-
P52 is protein that has the baility to stop cell cycle in the G1 phase
P53 is activated when DNA smages occurs. By stopping the progression into the 5 phase, p53
prevents damaged DNA from being replicated and passes on to daughter cells
In the DNA cannot be repaired, p53 activities teh cellular apoptosis program and the cell is
destroyed
Motion in the p53 gene prevents this safety switch from being turned on, and allows DNA
mutations to be passed on to the daughter cells. P53 mutations are found in virtually neoplasma
Another tumor suppressor gene is the breast cancer gene ( IE. BRCA-1). This protein is believed to
be involved in DNA repair. Mutation in this gene are found in rare breast and ovarian cancers.
Factors in cancer development ( carcinogene)
Genetic
- In 50 types of cancer altered oncogenes or tumor suppressor gene are inherited e.g; breast cancer
( BRCA1 and BRCA2) retinoblastoma
Biologic
- Chronic irritation and inflammation: associated with increase mitosis and cell transformation e.g;
colon cancer- ulcerative colitis, adenocarcinomas of the esophagus - barrets esophagus
- Age: many cancers are more common in edlerly perhaps due to increase number of rectaive oxygen
species ( free radicals) , deteririoting cellular reaction and poor nutrition
- Hormones; inadequate progesterone and estrogne - endometrial cancer; expression of estrogen
receptros in breast tumors ; testostrone may continue to prostate cancer
Bilogic
- Viruses; some have transforming properties where they alter host cell DNA e.g: hepatitis B virus (
HBV) and HCV– HEPATOCELLUAR CARCINOMA; herpes simplex virus 2 ( HSV-2) and human
papillomavrius ( HPV) cervical cancer ( eraly decataion with PAP smear)
Lifestle
- Smoking : cigarette smoke contains both inducer and promoter – cancer of the lung, larynx,
esophgus, pancreas, kidney, cevix and baldder
- Chewing tobacco: cancer of roal cavity and esophagus
- alchohol ; believed to enhance transport of carcinogens; exacerbates carcinogenic effects of
cigarette smoke- cancer of oral cavity and esophagus
- Diet: smoked, charbroilled, slated or otherwise preserved foods, foods fried in refused fat are
assocaited with gastric cancer; high fat, protien and beef or low fiber diets– colon cancer
environmental/chemical
- Many chemicals in the industrial workplace and in pollution have been identified as carcongoen;
asbestos, nickel- lung cancer, benzene- lukemia, anline dyes-baldder cancer- herbicides- non
hodgjins lymphoma
- Alos includes the chemical in food from preparation 9 see biological factors ) and cigarette smoke
Radiation
-
High energy radiation rays radioactive chemicals cause chromosomal ( DNA) damage; ultraviolet (
sun) rays- skin cancer; ionizing radaion - leukimia
Naming tumors
Tumros are named by a root–cell type of origin, and suffix -beningn tumor or malignant tumor of
specific tissue type
Roots
Suffixes
Examples
Fatty tissue- lip
beningn - oma
Lipoma: benign tumor of fatty
tissue
Gland tissue- adeno
Malignant epithelial tissue
Carcinoma
Adenoma: benign tumor of
glandular cells
Fibrous tissue- fibro
Malignant connective tissue
- Sarcoma
Adenocarcinoma: malignant
tumor of epithelial lining of a
gland
bone-osteo
Nervous tissue
Osteoma: benign mass of
lamellar bone
Osteosacroma: malignant
tumor of osteoblasts
Note
-
Oma- suffix is sometimes used for specific malignant tumors e.g: lymphomas and
melanoma
Staging of tumros
-
Staging is classification system that is useful in determining the prognosis of a cancer and
the most apropriate therpay
- Cancers are placed in one of four stages ( 1,2,3,4,5) where stages i tumors are small and
well localized and stage IV tumros are larger and have metastasized to other sites
Cancers are assessed according to the TNM system
- T : indicates the nature and the size of the primary tumor
- N: indicates the involvements of regional lymph nodes
- M: indicates the spread of metastasis of the tumor
The TNM score determines the stage of the cancer. The specific of this nomeclature are different
for every cancer
Cancer dignosis and managements
-
Serum analysis is used to detect tumor markers which are antigens expressed on the
surface of tumor cells or substance released fron normal cells in response to a tumor
- Serum analysis is ised for screening diagnosis estblishing prognosis, monitoring treatment,
detrecting recoccurnace
Include
- Hromoones and enzyme which are over expressed by the tumor e.g: the prostate specific
antigen ( PSA) which is released into the blood by prostate tumors
- Protien that are normally expressed during fetal development
- Genetic testing: the polymerase chain reaction ( PCR) is used to amplify DNA abnromlaities
specific to tumor cells which allows detection among small numbers of cancer cells
- Used for lukemia, lumphomas, meonomas, neurobalstoma and several carcinoma
- New research is related to the use of egne therapy where genes are introduced into the
pateins cells in attempts to correct the cells metbolsim , or destroy cancer cells
Cancer tretaments
-
Treatments of cancer involves surgery, chemotherapy or radition, pften a combination of
these is required
If cancer is known to be hromones sensetive hromones manipulation or hormone
antagonist drug may be of benefits
Biological therpay with interleukins and interferon can sometimes be used to increase the
activity of the immune systems to help destroy transformed cells
Nutritional supplementation is often useful to prevent malnuatition and show cachexia
Week 2 neoplasia
Lung cancer
●
●
Lung cancer is the number one cause of death d/t cancer
It has historically been more common in males and in most cases (> 80 %) have been
linked to smoking
● Highest risk is for those who begin smoking earlier in their lives, smoke heavily
● Second hand smoke has also been implicated in the risk of lung cancer.
Risk factors of lung cancer
- asbestos, polyvinyl chloride (PVC’s ) a nd some radioactive materials in mining and warfare
can cause local increases in lung cancer incidence. Industrial chemicalexposure in
combination with smoking greatly increases risk
Symptoms of lung cancer
- Symptoms of lung cancer may be d/t local effects of the tumour or they may be d/t
metastasis or paraneoplastic effects.
-
Local effects may include irritation and obstruction of airways: dyspnea, SOB, persistent
and productive cough and wheeziness of the chest • There may also be hemoptysis ; chest
pain ; voice hoarseness
- Tumour compression of the superior vena caca may causes swelling of the neck veins and
facial edema. Tumours near the visceral pleura may cause pleural effusion, pneumothorax
or hemothorax
Systemic effects:
-general fatigue, malaise, anorexia and weight loss
-
Prostate cancer
Benign
prostatic
hyperplasia
Breast cancer
Paraneoplastic effects result from tumour production of hormone-like secretions such as
compounds similar or identical to ACTH, ADH, PTH
PROSTATE CANCER
- This is a common form of cancer , the 2nd most common cancer in males, especially for
those > 50 years old. It is seldom seen in young males though in those cases where it does
occur at a young age the prognosis is often much worse ie. >60 % mortality within 3 years.
Predisposing factors include
- older age, incidence increases significantly after 5o
race/ethnicity , for example it is more common in the Afro-american population
- environmental contaminants , eg. exposure to the heavy metal cadmium
- exposure to oncogenic viruses
Treatments
- Surgery, chemotherpay and radiation
- Estrogen therapy
BENIGN PROSTATIC HYPERPLASIA
-
This increase in size and change in structure of the prostate is very common in males over 50 years
of age. The enlargement or growth is usually on the medial and lateral regions of the gland, thus
causing a narrowing or restriction of the urethra and a subsequent restriction of urine flow.
Manifestations( signs) include:
- hesitancy
- frequency
- reduced force of the urine stream
BREAST CANCER
This is the most common form of cancer found in females
Risk factors include:
Gender -much higher risk in females
Age - increased risk with increasing age - esp after age 50
Family history of breast cancer
Reproductive history eg . higher risk if nulliparous., delayed reproduction (eg. first • pregnancy after
age 30) , early menarche or delayed menopause.
Early Sign and symptoms of breast cancer include -
-
presence of a palpable mass on self examination or medical examination. These masses tend to be
firm but poorly defined, non-mobile (fixed) usually painless and singular. They are most common in
the upper outer quadrant.
nipple discharge
- nipple retraction or puck
Additional note on Breast Cancer - Two genes for breast cancer are known. Named BRCA1 and BRCA2 .
They account for about 5% of cases of breast cancer. Screening is available for these genes.
Fibrostic breast conditons
- Range of breast tissue changes that involve tissue masses that tend to respond to hormonal changes
throughout the menstrual cycle
Usually being more prominent and causing greater symptoms in the post- ovulatory or luteal phase
of the cycle
This condition is very common especially in women in their 30's or 40's and is the most common
cause of surgical procedures of the breast. These breast lumps are not precancerous and as such pose
no risk for breast cancer though they do need to be distinguished from cancerous masses •
- Usually well defined mobile round granular masses
- Usually detected on breast self examination or in routine mammography and often further
analysed using ultrasound and biopsy
Colorectal cancer
-
This cancer is has one of the higher mortality rates for cancers in those > 50 years old largely as a
result of too late detection
Predisposing Factors:
- Diet: a diet high in animal fats and refined carbohydrates, low in fibre
- This increases transit time and probably the increases exposure time to carcinogens
- Pre-existing conditions: such as familial multiple polyposis and ulcerative colitis
- Genetic (familial) factor
Signs and Symptoms:
Early S/S4 tend to be vague and may include changes in the bowel pattern such as periods of diarrhea and
constipation alternating. Early proctoscopic examination may reveal a small mass
Later there may be more distinct changes in fecal output including:'
diarrhea if the tumour is in the ascending colon or above
constipation if the tumour is in the descending colon or below
flattened or ribbon-like stools if it is in the sigmoid or rectum
occult (hidden) blood if it is more proximal –eg.the ascending colon
- frank (obvious red) blood if it is in the distal colon ( eg. rectum)
Late SIGN AND SYMPTOMS can include:
- the s/s of obstruction
local pain
- s/s of perforation and the resulting peritonitis
presence of a palpable mass that puts pressure on spinal nerves leading to s/s of nerve
compression such as sciatic and back pain, paresis and bladder dysfunction
- typical late cancer s/s such as cachexi
Week 3 notes : eye and ear disorders
Anatomy of the eyes
Anatomy of the ear
Glaucoma
- Disease in which there is a rise in intraocular pressure ( the pressure inside the eye) or IOP
- Pressure rises it is translated throughout the eye and it leads to compression of the blood
vessels that supply the retina
- Leads to retinal ischemia/ infarction and the result will be vision loss
- Glaucoma occurs as a result of obstructed outflow/reabsorption
-
There are two forms of Glaucoma:
Glaucoma
➢ Chronic or open glaucoma
➢ Incidence begins to increase significantly after age 50
➢ Gradually but progressive, symptoms are often not detected (asymptomatic) or they may
just involve very mild blurring of the vision and some haloing around lights and so it is a
major cause of vision loss
➢ As the IOP slowly rises there is loss of peripheral vision because initially the pressure
compresses mainly the smaller arteries and arterioles of the choroid that supply the
outer/peripheral retina
➢ Routine testing of peripheral visual field.
➢ Routine measurement of IOP
➢ Treatment is usually by using pharmaceuticals —however, the partially vision loss cannot be
restored
Glaucoma
➢ Acute or closed angle glaucoma
➢ Most commonly a result of a congenital abnormally narrow angle
➢ The iridocorneal angle is much narrower than normal so that in the event of a wide pupil
dilation the radial iris muscles contract and bulge in the middle and may contact the
cornea, adhering to it and effectively blocking the angle so that there is little or no aqueous
outflow
➢ IOP will rise rapidly leading to severe and immediate
Sign and symptoms of acute or closed glaucoma
-
such as photophobia, extreme corneal pain , redness of the eye, severe headache and
nausea , halos around lights , bulging cornea and of course a dilated unresponsive pupil.
This is a medical emergency and can rapidly lead to permanent and significant vision loss
(within 24-72 hours). The treatment may involve pharmaceuticals
Cataracts
• Involves an opacity or loss of transparency of the lens
Possible causes of cataracts include:
• Senile cataracts associated with aging
• Traumatic cataracts can result from trauma
• Chemical cataracts as a result of exposure to a wide variety of industrial chemicals
• Metabolic cataracts which are most commonly a result of diabetes
• Congenital cataracts which may result from in utero exposure to infections such as rubella or
toxoplasma or to chemicals or episodes of hypoxia
Treatments of cataracts
-
usually involves removal of the lens and replacement with an artificial intraocular lens
Detached retina
• Associated with aging d/t gradual shrinkage of the vitreous or with an episode of sudden
deceleration that created torsional movements in eye and leads to a tear in the retina
Signs and symptoms of detached retina
-
can include a perception of a dark curtain moving across the visual field; flashing lights and
a high incidence of “floaters” in the visual field
Usually no pain associated with this but it must be corrected immediately to minimize the
degree of permanent vision loss
Hearing loss
• Hearing loss can result from damage anywhere along the pathway but some losses are very
common and a result of typical human activity.
• Exposure to very intense sound waves – either single events of extreme intensity or prolonged
exposure to high intensity
• Workplace noise exposure
• Inflammation associated with middle ear infections can also lead to hearing loss by forming
a scar
Nervous system
-
The CNS is is protected by structures including the skull, spinal vertebrae,
meninges, and cerebrospinal fluid
CSF
-
Flow: Lateral ventricle → third ventricle → fourth ventricle → central canal of spinal cord →
subarachnoid space
- Production; SF is produced mainly by a structure called the choroid plexus in
the lateral, third and fourth ventricles
Cranial nerve and functions
Spinal plexuses and integrative pathways
I
Anatomy and physiology of neurons
ANS ( autonomic nervous system)
Function
- is a component of the peripheral nervous system that regulates involuntary
physiologic processes including heart rate, blood pressure, respiration, digestion,
and sexual arousal.
Divison
- Sympathetic -arouses the body and loses energy ( actiavtes the fight and flight
mode)
- Parasympathetic- state of calm and it retsores energy
- Enteric
- Veins that are swollen, red, hard, or tender to the touch
- Veins that are llen, red, hard, or tender to the touch
- Veins that are swollen, red, hard, or tender to the touc
week 4 notes : neurological disorders
-
ascow coma scale
- the glasgow coma scale ( GCS) is a neurological scale wich aims to give a reliable and objective way
of recording the conscious state of a person for initial as well as subsequent assessment
1
2
3
4
5
6
Eye
Does not
open eyes
Opens eyes
in response
of painful
stimuli
Opens eyes
in response
to voice
Opens eyes
spontaneo
usly
N/A
N/A
Verbal
Makes not
sounds
Incompreh
ensible
sounds
Utters
inappropria
te words
confused ,
disoriented
Oriented,
converses
normally
n/a
Motor
Makes no
movement
Extension
to painful
stimuli (
decerebrat
e response)
Abnormal
flexion to
painful
sti,uli (
decorticate
response)
flexion/wit
hdrawal to
painful
stimuli)
Localized
painful
stimuli
Obeys
commands
Intracranial pressure
Elavated ICP S/S
● Decreased in levels of consciousness
● Headache
● Nausea and vomiting
● Vision changes:
A. fixed dilated and unresponsive pupils
●
B. papiledema
●
C. strabismus
●
● CVS changes
● - changes in temperature regulation
● - changes in respiratory control
● - changes in the CSF
● – seizures
●
Common lesions/ herniations of the brian
- Supratentoral: lesions are those that develop above the tentorium cerebellum
-
Infratentorial lesions: are those found below the tentorium cerebelli can lead to
eraly effects on the brainstem
Hydrocephalus
-
-
Hydrocephalus involves an accumualtion of cerebral spinal fluid
There are two main forms
A. communicating hydrocephalus decrease of outflow of CSF from the
subrachnoid villi. This could be d/t
i) a congenital deficit or abnromally of the arachnoid villi
ii) an obstruction of the arachnoid villi as a result of accumulation of infection
debris
iii) obstaruction as a result of scarring formed
B. non-communiacting or obstructive hydrocephalus- in which there are an
obstruction of outflow from the ventricaulr system out into the subarachnoid space
could be d/t
i) a congenital deficit or abnormality of some aspect of the ventrucaulr system
ii) an obstruction of the ventricles or cerebral aquaduct as reuslst of tumor
compression
iii) traumatic damage to the ventricles or aqueduct
iv) infection leading to obstruction
Coma and brian detah
-
Loss of consciousness and coma can result from a wide variety of causes- both
intracranial and extracranial
Some extracranial causes can include:
-
Metabolic changes such as hypoglycemia, uremia, diabetic ketoacidosiss, hepatitis
and hypothyroidism
Respiratory problem leading to hypoxia
Drug intoxication including alcohol, opiates and barbituates
Carbon monoxide posioning
Shock ( eg, acrdiogenic, septic etc)
Hyperthermia
Some intracranial causes include
-
Meningitis
Epilepsy
hemorrhage , aneurysm etc. in the cerebral circulation
CVA’s
Cellular injury
-
Clinical death: is the absence of vital signs. There is no measurable respiratory or
cardiac activity to sustain body functions and no movement
Brain death or neurological death: for this to be declared the following criteria
m ust be observed
No spontaneous meovements including seizures for a period of at least one hour
No brainstem reflexes that can be elicited including
-
No papillary reflexes ie. fixed dilated and unresponsive
No gag reflex
No vestibule occurla response to cold water
exclusion criteria: before brain death can be declared the following ruled out:
-
hypothermia: ( ie. body core temp <32.2 c)
drug intoxication
metabolic and endocrine distrbances as hypoglycmice and metabolic acidosis
HEAD TRUMA
-
Can lead to two levels of brian damage -primary and secondary
Primary brian damage is the direct result of the trauma and might include
compression or laceration damage to brian tissue
Secondary brain damage could result from
-
Inflammation leading to elevated ICP
Infection of brian tissue
Disruption of blood flow as a result of damage to blood vessels leading to ischemia
for bria tissue
Disturbance of respiratory function d/t factors such as airway obstruction or
altered resp. Control by damage to the medulla and pons
Post truamtic syndrome
-
NOTES
The effects may last for days to months to years and can iclude manifestations such
as
Hedacahe, vertigo, irritability, memory deficit, decreased ability to concentrate,
sleep disturbance, emotional lability, a variety of phobias and behavioural changes
Primary barin injury
●
●
-occurs as a direct reuslt of the initail insult
Over so rapidly limitation for prevention
Secondary injury
❖ Progressive damage reuslting from the bodys physiologic response to the initial insult
❖ Occurs over time cen be prevent high mortality and morbidity
Critical factor in determining the neuroal cell fate fater injury
-
Degree of adenosine triphosphate (ATP) depletion
Mechanism of brain injury
-
Ischemia and hypoxia
Ischemia- decreased blood flow
Primary insulty —---------> inability of neurons to egnerate ATP
-
Secondary response —---> oxygen free radical excitatory a.a inflame cells —---> hydroxyl
radicals superoxide peroxide
Hypoxia- decreased oxygen at cellular level
Ischemia and hypoxia usually occur together
Cellaulr energy failure
-
Neuronal tissue highly sensitive to oxygen deprivation 5-10 mins without oxygen —>
irreversible brain damage
Great ATP requirement and limited capacity for anaerobic
DEPENDENT ON GLUCOSE for ATP production
Store very LITTLE GLYCOGEN
TWO MECHNISMS CAN CAUSE BRIAN CELL DETAH:
Anaerobic metabolism
Mitochondrial dysfunction: —--> anaerobic glycolytic pathways —> puruvate converted to
lactate—> hydrogen ions—--> cellular acidosis
Deterioration of ion gradients; K+ efflux, NA+ Cl-Ca2+ influx
Excitatory amino acids
●
●
●
●
Excessive glutamate may be released because of imapired membrane integrity
Repuatke mechanisms fail to remove excess g;utamte because they are energy dependent
processes
Excess glutamate stimulates nearby neurons that then take uplarge amounts of injurious
calcium ions: calcium overload injury
NMDA receptor activation stimulates nitric oxide production in neurons in excess it
may increase the production og reactive nitrogen species that function as free radicals to
damage cellular components
Reperfusion
Oxygen reenters cells, unpredictable transfer of electrons to oxygen can produce reactive
oxygen products that behaves as free radicals ( hydroxyl radical, superoxide peroxide)
Cell membranes may undergo LIPID PEROXIDATION in response to free radical damage
with subsequent formation of arachidonic acid
Week 5 notes: neurological disorder
Cerebral circualtion
- The anterior cerebral artery supplies the anterior frontal lobe ( for higher cortex functions
personality, reason, judemnet, etc)
- The medial and superior aspect of posterior frontal lobe including the motor cortex for
control ove the lower body ( pectroal gridle)
- The medial and superior aspect of the anterior parietal lobe including the somatosenspory
cortex for the lower body
The posterior cerebral artery supplies: the occipital lobe including the visual sensory
visual association area
- The middle cerebral artery supplies: the alteral anterior frontal lobe which is responsible
for motor control over the upper body- face, pectroal girdle, thorax
- The lateral anterior parietal lobe which is responsible for somatosensory function
- For the upper body
- Most of the temporal lobe including the auditory sensory areas
- The left middle cerebral artery supplies the blood flow for the broca’s ( speech motor ) area
for wrenicke’s ( speech comprehension ) area
Blood brain barrier
- Capplireis here frim tighter junctions with a thicker basement membrane layer and an
interaction with astrocytes
- Prevent wider swings in ion and hormone and nutrient level that occur in the rest of the
bodies ECF from occuring in the brain ISF
- Prevent the entry of many toxins into brain tissue
- Prevents entry of most pathogens into brain tissue
Cerebral vascular occlusive disease
- There aere a vriety of vsaculr pathologies that can cause focal ischemia and infraction of
brai tissue including
- A) local cerebral vessel obstruction such as atheroscelrosiis which then promotes local
thrombus formation
- B) remote origin emboli. Thromboemobliusm ( or gas or fat emboli) may be formed
elsewhere in the bidy esp in the herat and these travel through the vessels until they lodge
somewhere in the cerebral circaultion
Cerebral aneurysms
- c.) cerebral aneurysms
- Most common occur at the area around the branching of a major artery where the vessel
wall is intrinsically weaker
- Occurs in the high pressure interconnections of the circle of willis and as an aneurysm
enlarges it occupies space which will increase ICP
- Altered flow will increase the risk of a thromembolsim
-
If they rupture —---> large volume blood loss leading to severe cerebral ischemia and the
development if large volume hematomas ( especially leaking into subarachnoid space)
Cerebral vascaurl accidents
-
A CVA or stroke describes the acute neurological deficit these processes produce. CVA’s are a major
cause of death and permnante fucntion deficit
Risk factors predisposing to CVA’s include
1. Non modifiable factros: older age, lipid abnormalities, elevated librnogen levels, systemic
hypertension, diabetes, sickle cells disease, polyethemia, and atrial librillation
2. Modifiable risk factors include: use of alcohol, smoking, amphetamines, cocaine as well as obesity,
edentary lifestyle and oral contarceptive use
Meningitis
- Meninges are inflamed
- Escherichia coli
- Streptococcus pneumonia
- Hemophilus infulenzae
- Neisseria meningitis
S/S of becatreial meningitis
- Fever
- Severe headache
- Nause and vomiting
- Nuccal rigidity ( neck stiffness) and often plan in the back, abdomen and extermeiteis
- Kernigs. Signs - resistance to extension at the knee while lying on teh side with the hip
flexed
- Brudzinski’s sign– flexion at the neck result in flexion at the hip and knee
- Direct result of inflammation of the meninges and the pain associated with it. Many
movements tug at the meninges anbd elcit pain
Encephalitis
- Inflammation of the berain. There are several causes, but the most common is a viral
infection
- Encephalitis often causes only mild flu-like signs and symptoms — such as a fever or
headache – or no symptoms atr all. Somtimes the flu like symtpoms are more severe.
Encephalitis can alos cause confused thinking, seizures, or problem with movement or with
senses such as sight or hearing
- In some cases, encephaultis can be life thretahening. Timely diagnosis and treatment are
importa because its difficult to predict how enecepahlitis will affect each individual
- Most people with viral encephalitis have mild flu-like symptoms such as
- Headache
- Fever
- Aches in muscle or joints
- Fatigue or weakness
-
Sometimes the sign and symptoms are more severe and might include confusion, agitation,
or hallucination
- Seizures ‘loss of sensation or paralysis in certain area of the face or body
- Muscle weakness ‘problem with speech or hearing
- Loss of consciousness ( including, coma)
In infants and young children, sign and symptoms also includes
- Bluging the soft spot ( fontanels ) of an infant’s skull
- Nause and vomiting
- Body stiffness
- Proof feeding or not waking for a feeding
- Irritability
Week 6 neurological disorder
Spinal cord injury
- A complete spinal cord injury at a specific site there will be loss of control over functions
affected by the nerves and tracts of that location and everywhere below it
- Many spinal cord reflex functions below the injury site may remain intact but any voluntary
control these reflexes will be lost
- Reflexes will be lost if they are at the immediate injury site
- The permnanent effects the injury will depend on where the spinal cord damage occurs as
indicate the following
- C1-c2 ( spinal cord segments) some or no control over the neck and head movement and
there will be quardiplegia. No diaphragm control since the phrenic nerve is located at c3-c5
so the individual will require immediate and continuing mechanical ventialtions
- C5-c6 full neck and head control and some shoulder control. If at c5 then there may be
flexion at the elbow. If at c6 possibly some wrist control and no control over the lower limbs.
There is complete diaphragm control so no assistance with ventilation is required
- T5: full hand and finger control and the use of intercostals muscle for breathing but there
will be no SNS control over vasomotor function
- T6: there will be abdominal muscle control but still no control over the lower limbs
- T7 good SNS control over vasomotor function
- L1-L3: there will be hip control and the ability to do knee extensions
- S2-s4 there will be leg to ankle control and voluntary control over bowel and bladder
function as well as sexual function.
Compliactions of SCL
- Spinal shock
- Autonomic dysrellexia
- Edema and deep vein thrombosis d/t blood pooling as result of decreased SNS vasomotor
contro and the immobility
- Decubitus ulcers and joints contractures d/t the immobility
- Increased risk of further injury d/t a.) spstic motor control involving jerky motions that makes
falling and other injuries more likely and b) loss of sensory function causing decreased
awareness of harmful stimuli
- Hypotension ( postural d/t lack of SNS regaultion of vasomotor response leading to fainting
when trying to rise
- Paralytic ileus
Seizure disorder
-
General tonic clonic seizures or grand Mal Seizures, these are the common from of
seizures and they take classic form usually associated with seizures in which there is the
loss of consciousness and tehre are convulsions
- Can be preceded by a prodromal elect referred to as an aura. The aura may involve visual,
auditory or olfactory or even motor effects. ( recall the burnt toast eg) however in many
cases the individual has no warning and directly enter the tonic phase
- The postal ictal or recovery phase often begins with flaccid coma like state d/t
neurotransmitter exhaustion
Status epilepticus
- Series of seizures in sucession with no break for recovery between them and often with no
regaining of consciousness between seizures. There are considerable risks d/t acidosis,
hypoxia, hypoglycemia and fever. This can lead to cardiac arrest. Respiratory and or detah
of the possibility of permanent brain damage
Dementia
- Dementia is a disorder that is charactrized by a decline in in composition involving one or
more cognitive domains ( learning and memory. language , excessive function, complex
attention, perceptual motor, social cognition) ( 1)
- The deficits must represent a decline from previous level of function and be severe enough
to interfere with daily function and independence. The most common form of dementia in
older adults is alzheimer disease acconting for 60 to 80 percent of cases
- Mild cognitive impairment is an intermediate clinical stage between normal congition and
dementia. While specific subtle chnages in cognition can occur in normal aging, MCI cal
also be a precursor to dementia. At the same time, MCI may alos represent a reversible
condition in the setting of depression, as a complication of certain medications, or during
the recovery from an acute illness.
- As the population ages, the overall burden of dementia is increasing worldwide. With an
aging population and growing awareness of AD and other late life dementias, clinicals
should be equipped to test for cognitive impairment and ask about functional decline to
avoid failure to recognize casses of AD and related dementia. Clinicals will need to
accurately digbose and manage the eraly cognitive manifetsiaon of AD and other
dementias
The most common neurodegenerative conditions causing demntias are
- Alzheimer disease
- Dementia with lewy bodies: one of the most common type of degenrative dementia,
second to alzheimer disease. In addition to dementia, distinctive clinical features include
visual hallucinations, parkinsonism, cognitive fluctuatic, dysautonomia, sleep disorder and
neuroleptic sensitivity
- Frontotemporal dementia : group of clinically and neuropathologically heterogeneous
neurodegenerative disorders chracterized by prominent changes in social bhevaiour and
personality of aphasia accompanied by degeneration of the frontal or temporal bone
- Parkinson disease dementia
Parkinson disease dementia ( pdd)
- Cognitive dysfunction is common in parkinson disease and exists on a continuum of
severity prevalence increases with the duration of the movement dsorder. When severe,
dementia often surpasses the motor features of PD as a major cause of disabi;ity and
mortality
- While PD can coexist with other common cause of dementia, such as alzheimer disease
and vscaulr dementia, mild cognitive impariment and dementia are increasingly recognized
as common features of PD itself. The clinical characteristic and course of current
investigation.clinical features can generally distinguish between PD and other movement
disorders associated with dementia, such as dementia with lew bodies or progressive
suprenuclear palsy. However, whether PD dementia and DLB are distnct disorders, or
whether they represent different presentation of the same disease, is an area of debate and
investigation.
Alzheimers disease
- The basic pathological chnages that occur in alzheimers disease involver atrophy of the
cerebral cortex with neurons being lost especially in the frontal and temporal lobes
- The diagnosis of alzheimers is difficult since it is S/S can be confused with depression,
tumor of brian injury, nutritional deficiences, sevre anemia or durg toxocoties
- Protein makers associated with the disease shw promise as eraly dignostic tools
- Alzheimers can appear at any age although the frequency increases with increasing
- The disease is progressive moving through stages of severity
ALZHEIMER’S DISEASE
- Stage 1: S&s include eraly cognitive changes with mild mental impariment ( loss of
intellectual function) this may involve forgetfulness of recent events of being overwhelmed
by simple tasks succh as banking or sorting change when shopping
- Stage 2: this stage generally involve imapired judement and the this can lead to a need for
constant supervision. Memory loss increases so that basic information such as address and
phone number cant be recalled. There is often changes in behaviour so that often
inappropriate social behaviour, agitation/irritation and repetitive behaviour patterns.
- Stage 3; in this stage there is often a loss of bowel and bladder control ( incontinence) as
well as a lack of interest and inability for personal hygiene and self care.
Parkinson’s disease
-
The pathophysiology of this disease involves a dcrease in the neuron production of the
neurotransmitters dopamine ( or its precursor l dopa )
-
The causes of primary parkinsons are unknown ( idiopathic) primary parkinson’s occurs most
commonely in the elderly ( after age 60)
Secondary parkinson’s can be linked to:
-
Carbon monoxide poisoning and variety of chemical exposture’s An episode of encephalitis
Post truma to the head ( recall mohammed ali the famous boxer and other boxers)
Cerebral vascualr disease of other neurodegnrative diseases
Exposture to some antipsychotic/tranquilizer drugs such as chlorpromazine
Parkinson’s disease
- Menifestaion of this disease are inietially insidious with a gradual slowing of
movement and some muscle weakness but it is relentlessly progressiv.
Multiple sclerosis
- Problem of demyeliation of the axons of neurons
- The demyelination occurs in a ptchy distribution and where the myelin
sheathdegnerates is still leaves the axons intact but now the rate ( and efficiency) of
nerve impulse conduction is greatly reduced
- The effects is as if impulses were not conducted so that there will be function loss
that depends on which nerves are affected
- Wide range of possible signs and symptoms making the disease more difficult to
diagnose
Risk afctors for M.S include:
-
GENDER: ie. about 2x more common in women
AGE: ie. more common in the middle years -over 15 And under 55 years of age range
GEOGRAPHY: the incidences is highest in white and more affluent population in
temperature climate zone such as in n.e north america ( great lakes region) northern
europe, new zealand and australia- for unknown reasons.
- Genetics: there is a higher incidence within some families and there are autoimmune
aspects to the disease
Eraly manifestaions
- Transitory diplopia, blindness, blurry vision or scotomas
- Motor effects such as muscle weakness and tremors
- Sensory effects shc as paresrhesia
- fatigue , emotional swings
- Bowel or baldder problems such as urgency, frequency and constipation
Intermediate manifestaion include
- Speech problems
- Increasing visual problems
- Worsening, bowel and bladder problems
- Decreased muscle control and strength leading to a general decreased in mobility, altered
- Gair, muscle spasticity and contractures
- Reduces sexual fucntions such as impotence in men
Late maniifestaions include
- Reduced mobility or immobility leading to decubitus ulcers. Contractures
- Speech impairment/ communication problems
- Blindness
- Increased risk of respiratory infection
- Incotinence
- Depression and other emotional problems
Cerebral palsy ( CP)
- Cerebral palsy occurs at the rate of about one to five cases per 1000 live births, it involves
brain damage causing neuromuscaulr disability. This may involve damage to the motor
cortex, basal nuclei, cerebellum, pyramidal tracts or extrapyramidal tracts. It may involves
all degrees of motor deficit ranging from minor coordination loss or loss of muscle tone to
severe disability with muscle paralysis. Cerebral paslsy is not a progressive disorder.
Causes of cerebral palsy
- 1. Problem in letal development
- 2. Birth injuries that lead to anoxia ( lack of oxygen) ischemia
- 3. Anoxia neonat orum- occuring in the period from birth to the end of the fourth week post
partum
- 4. Problem in infancy
S&S- effects on mobility
- In infancy there is often a decrease in muscle tone and a delay in motor development from
what is normally expected
- Muscle spasticity
- Athetosis
- Anaxic movement
Week 7
Burns
-
Injuries to tissues caused by contact with dry heat, moist heat,
electricity, chemicals, friction, or radiant and electromagnetic
energy
Burn injuries influence a variety of systemic, circulatory and
metabolic changes
Integumentary, cardiovascular, respiratory, thermoregulation and
metabolic, renal, immunity, psychological
Children and elderly more susceptible, also those of lower
scocioeconomic status
Terminal injuries
Integument Effects
Skin is largest organ of the body constituting 20% of body
weight
Three zones of injury described in burn wound
Necrosis is the area in the burn wound where coagulation necrosis
has occurred
Zone of stasis is a region of decreased blood flow that is
reversible with adequate resuscitation
Zone of hyperemia comprised of minimally injured tissue that
usually recovers normal function
Depth Classification
Divided into four classifications based on American Burn Association criteria
First degree
Superficial; outer epidermal layers
Second degree
Superficial partial thickness (epi and parts of dermis) and deep
partial thickness (entire dermis)
Third degree
full thickness (entire epi, dermis and subcutaneous)
Fourth degree
full thickness with bone or muscle involvement
First degree burns
●
●
●
●
●
Involve only outermost layers of the epidermis
Signs and symptoms: local discomfort, erythema, HA, chills,
nausea and vomiting
Typically self-limiting, healing in 3-6 days
e.g. mild sunburn
Second degree burns
Superficial Partial-Thickness Burns
●
●
●
●
●
Involve the epidermis to the level of the dermis
appear red to pale ivory; blisters, pain
Injuries typically heal in 7-21 days in the absence of wound
infection
Hair typically reappears
Deep Partial-Thickness Burn
●
●
●
●
●
●
Involve entire dermis
Mottled appearance
large areas of waxy-white tissue surrounded by light pink or red
tissue; flat, dry blisters, edema, pain
Usually excised early and treated with skin graft to diminish
scarring and achieve early wound closure
Third and fourth degree bruns
Third-Degree Burns
●
●
●
●
Involve epidermis, dermis, and underlying subcutaneous tissue
Appear white, cherry red or black, with deep blisters
●
●
●
●
●
Wound has dry, hard, leathery texture
Extensive edema; no pain
Often require skin grafting
Fourth Degree Burns
●
●
●
●
Full-thickness injuries that extend beyond the dermis to involve
muscle, bone, or both
Often occur in victims of high-voltage electrical injury or those with
prolonged exposure to intense heat
Terminal injuries
●
●
●
●
●
●
●
Besides depth, extent of injury is also important
Refers to percentage of total body surface area (TBSA) burned
Rule of nines used to calculate rough estimate of TBSA
involved
Lund and Browder chart is more precise
Includes consideration of age and anatomic part
Minor, Moderate, Major
Burn Shock and Acute Resuscitation
●
●
●
●
●
●
●
●
●
Capillary leak occurs within minutes and persists for 24 hours
fluid lost in the area of the burn and internally collects in nearby soft
tissues causing interstitial edema
Rate and volume of fluid lost directly related to severity of burn
Necessitates fluid and colloid replacement
Immune Response also contribute to burn shock
Cytokines act directly on the burn wound and activate agents that cause
further local and systemic inflammation; multisystem organ failure
Fluid and fibrinogen leave the dilated, permeable vessels
System complaoctions of terminal bruns
Cardiovascular Dysfunction
-
CO drops (reason unknown); vital organ perfusion is impaired
Metabolic Response
- Stress of burn and release of epi, NE increases MR, heat, nutritional
requirements
Renal Dysfunction
-
Hypovolemia causes renal dysfunction
-
Nephrons also damaged by myoglobin, drugs
-
Decreased peristalsis; gastric ischemia and stress → acute peptic ulcers
GI
Immunity
-
Sepsis is a significant complication
- Loss of skin barrier and invasive monitoring equipment
Respiratory dysfunctions
- Acute lung injury is the result of obstruction (bronchospasm
- and edema), inhalation of toxic fumes and thermal injury
- Inhalation injury results in chemical denaturing of pulmonary
- tissue and edema
- Onset within first few hours but clinically manifests 2-4 hours
- later
- Acute respiratory distress syndrome (ARDS) usually seen
- within 6 days
Elemental of burn injury survival
● Meticulous wound management
● Adequate nutritional support to establish positive nitrogen
● balance
● Early surgical excision and grafting of full-thickness wounds
Wound healing
● Main concerns are flexor
● contractures, excessive scarring,
● and keloid formation
● If adequate range-of-motion
● exercises are not instituted early in
● hospital course, new tissue will
● shorten and contracture will result;
● therapy aimed at extension of body
● parts
● Scarring is genetically inherited
●
●
burn garments prevent hypertrophic
scarring
Term 2
GI pathology
Liver function;
The liver doesn’t look spectacularly complex in structure but in fact it is an extremely complex
organ with a huge array of enzymes etc. that allow it to carry out a very wide range of funtions
including;
In CHO metabolism; it can do
i. glycogenesis - building glycogen from excess blood glucose especially immediately after a meal
ii.
glycogenolysis. Between meals as blood glucose levels fall it can convert the glycogen it
has stored back into glucose to maintain blood [glucose]
iii.
gluconeogenesis. When fasting and after the stored glycogen has been used up the liver can
convert nonpCHO’s such as lipids and proteins into glucose to maintain blood [glucose]
iv.
overall it has a critical role in maintaining the blood [glucose] under regulation by insulin
and glucagon
in Protein metabolism;
-synthesis of the blood proteins including the clotting proteins ( prothrombin, fibrinogen
and the factors), albumins ( for maintaining blood OP) and globulins (transport proteins) as well as
complement proteins that are necessary for immune function.
1.
Deamination which involves removal of the amino group from amino acids so that the
remaining carbon skeleton can be used to build many other molecules including CHO’s and
fatty acids. The amino group is a toxic nitrogenous waste and so the liver converts it to water
soluble urea so that it can be eliminated by the kidney.
2.
Transamination which allows the liver to convert any nonessential(12) or any essential (8)
amino acid into any other non-essential amino acid so that in this way in spite of whatever
proteins were ingested the liver will be able to ensure that the amino acid profile that circulates
in the blood to the tissues will be the optimum for protein synthesis functions.
In Lipid metabolism;
- lipolysis. The liver can break down lipids for use as an energy source of to do gluconeogenesis
- lipogenesis. The liver can synthesize many lipids including triglycerides ( for storage), HDL’s
and LDL’s ( for transport) and cholesterol. Lipid production of cholesterol is critical because it is
used for many functions including as a membrane component, for bile salt production and as a
necessary precursor to the synthesis of steroid hormones such as aldosterone, corticosteroids,
progesterone, testosterone and estrogen.
- in Storage; The liver can store glycogen, triglycerides, all the lipid soluble vitamins (A,D,E,K)
and vit. B12 as well as iron as ferritin (bound to a protein) or transferrin ( for transport to the
bone marrow)
- Detoxification. The many enzymes it has allows it to break down a wide range of chemicals that
may have been ingested accidentally or produced by bacteria as well as many drugs and even
alcohol. Thus it reduces risks of toxic destruction of tissues
- Regulation of hormone levels in the blood. Most hormones can be broken down by the liver so
that they cannot accumulate in the blood.
- Removal of pathogens and foreign materials that enter the blood via the GI tract. Specialized
phagocytic cells called Kuppfer cells line the liver sinuses ( as reticuloendothelial tissue) and
engulf foreign cells as the percolate through the liver - preventing them from entering general
circulation. Note that all blood flow from the GI circulation ( splanchnic circulation) must first
go through the hepatic portal vein and thus through the liver before entering general circulation.
This way the liver can adjust everything about blood chemistry before it reaches the other
tissues.
- Destruction of worn out red blood cells (RBC’s) occurs in the liver. THe iron in heme of
hemoglobin is stored as ferritin for reuse, the globin protein is broken down into amino acids
for reuse and the piment in heme which is toxic is converted to conjugated water soluble
bilirubin and added to the bile so that it can be eliminated in feces ( turns them brown)
- The liver synthesizes bile salts which it adds to the bile. These salts are responsible for
emulsification of fats (mechanical digestion - making large globules into smaller globules) so
that lipase enzymes can act more effectively to chemically digest the fats.
Jaundice.
This term refers to the yellowish-bronze colouration of connective tissue in the skin and other
locations d/t the accumulation of bilirubin pigment that is produced when hemoglobin is broken
down. It is usually most obviously seen in the sclera of the eyes. There are three main ways for
jaundice to develop;
Prehepatic jaundice; This involves the excessively high rate of RBC destruction so that , although
the liver function is normal it is unable to completely process the high levels of bilirubin produced ie. it is unable to completely conjugate it all into a water soluble form so that blood levels of both
conjugated and unconjugated bilirubin will rise. The main causes of this will be ABO and Rh blood
incompatabilties (eg. transfusion reactions), Malaria and sickle cell disease.
Manifestations will include hyperbilirubinemia ( conjugated and unconjugated), dark coloured
feces ( d/t high bilirubin level eliminated via the bile into the small intestine) and dark urine ( d/t
high levels of the bilirubin in the feces being reabsorbed and then filtered out via the kidneys).
There will also be the typical s/s of anemia d/t the destruction of RBwC’s.
Posthepatic jaundice; This is a result of an obstruction of the biliary tract ( eg.t he common bile
duct or the hepatic duct or the outlet of the common bile duct into the duodenum. Typically these
obstructions occur d/t obstuction by gall stones (cholelithiasis) or inflammation of the duodenal
mucosa d/t alcohol abuse. In these cases the bile is unable to enter the duodenum and so backs up
toward the liver.
Manifestations include pale stools ( since bilirubin doesn/t reach the SI), dark urine ( the bilirubin
re-enters the blood and is filtered out by the kidney) , hyperbilirubinemia (conjugated) and
steatorrhea which is seen as fatty/oily/greasy and often foamy stools as a result of greatly reduced
fat digestion since the bile salts necessary for fat emulsification are not reaching the SI from the
liver. Often this lack of fat digestion leads ot inadequate absorption of vit.K produced by the gut
flora and so since the vit.K is needed for clotting protein production by the liver there will be
bleeding disorders. There may also be severe pruritis since the bile salts are not secreted so instead
they will enter the blood and irritate skin and other tissues.
Hepatocellualr or intrahepatic Jaundice; This involves some problem with the liver itself which
could be d/t infection by viruses or bacteria or exposure to toxins including some drugs ( eg.
acetaminophen) or alcohol or environmental toxins leading to liver inflammation or hepatitis. In this
case the liver will not be able to carry out many of its critical functions and there will be many
serious manifestations including;
- hyperbilirubinemia ( unconjugated) and obviously pale stools and urine
- hormone imbalances since the liver will not be breaking down hormones they will accumulate to
high levels. There are many possibilities here but some common effects include gynecomastia (
enlarged breasts in males d/t accumulated adrenal estrogens) hirsutism ( increased hairiness in
females d/t accumulated adrenal androgens), cushings syndrome ( d/t accumulated aldosterone
and glucocorticoids) etc. etc.
- increased episodes of drug overdose and other toxicity reactions because of decreased liver
breakdown of drugs
- decreased fat digestion d/t decreased liver bile salt production leading to some steatorrhea and
decreased vit.K absorption
- much wider variation in blood [glucose] and amino acid profile as a result of decreased liver
ability to carry out the wide range of chemical reactions necessary.
With hepatocellular jaundice you may see hemorrhagic symptoms because the livers
functions have been directly compromised by a liver pathology so that it's capacity to
produce prothrombin, fibrinogen and other clotting factors may have been reduced.
With post hepatic jaundice
-
liver function may be normal but since no bile is reaching the duodenum then fat
emulsification, digestion and absorption will be reduced and so the absorption of fat
soluble vitamins such as vitamin K will also be reduced. Vit. K is essential for
prothrombin synthesis in the liver.
Hepatitis
Hepatitis is an inflammation of the liver. It can occur as a result of a number of causes
including bacterial or parasitic infection , chemical toxicity by chemicals such as alcohol,
acetaminophen, many solvents etc. or by viral infections.
There are quite a few forms of viral hepatitis including;
Hepatitis A : Also referred to as HAV it is an RNA virus. Hep A is the most common
viral hepatitis and though the incidence is declining in North America it still very common
worldwide , especially in the developing nations.
The mode of transmission of Hep A is the fecal oral route which usually means that it is
found in contaminated water, milk and a wide variety of foods such as vegetables that
have been grown using fecally contaminated irrigation water or exposed to contaminated
dust. It is often also associated with shellfish which are filter feeders and accumulate the
virus from contaminated waters. It is also possible to transfer the virus in anal-oral sex.
Young children (under 7 years old) are often completely asymptomatic when infected.
People at greatest risk include tourists to the developing countries where sanitation may
not be as effective, child care workers (ie. dealing with young children and their diapers),
health care workers ( when handwashing is inadequate).
The usual incubation period is 2-6 weeks and the individual can be infectious 2 weeks
before showing jaundice or other s/s. The signs and symptoms involve an acute hepatitis
with a mild fever, vomiting, anorexia , fatigue and malaise (ie. typical signs of most viral
infections) along with hepatomegaly (enlarged liver) and , of course, jaundice. Usually
recovery is quite rapid and there are almost never any long term effects such as chronic
hepatitis or cirrhosis. Very rarely hepatic failure may occur. The virus seems to be
completely cleared from the system and the individual now has life- long resistance. A
vaccine is available and is highly recommended for anybody doing much international
travel.
Hepatitis B : also known as HBV is different from the other viral forms of hepatitis in
that the virus is a DNA virus. It is quite common and a far greater risk than Hep A. The
virus is transmitted in body fluids. Primarily it is transmitted in blood and blood products. It
has become much less commonly transmitted in blood transfusions because of effective
screening but it may be associated with surgical accidents or other exposures to blood
such as needle stick injuries, shared (reused) needles, shared razors or piercing tools etc.
The virus can also be found in saliva , semen and vaginal secretions (and to a lesser
extent in tears and urine) so it cn be transmitted by sexual activity. Those at most risk
include intravenous drug users, long term male prisoners, frequent recipients of blood
products, recipients of dialysis treatment, gay males and health care workers such as
nurses, doctors, dentists and hygienists.
The incubation period ranges from 1-6 months .One problem with HBV is the high
frequency of asymptomatic carriers ( about 50%) and the other problem is that a certain %
of cases (around 10 % ) develop chronic hepatitis that may progress to cirrhosis and
others will go on to develop hepatic cancer. There is a Recombinant DNA vaccine that is
available and it is routinely given to health care workers and school age children.
Hepatitis C or HCV:
This is a single-stranded RNA virus which is primarily transmitted via the blood so the
highest risks are associated with blood transfusions, intravenous drug use and
needle-stick injuries. Other body fluids don’t seem to be a risk. HCV can manifest as an
acute or chronic disease but typically it is chronic and slowly progressive and creates a
significant risk of liver cancer (hepatocellular carcinoma) and cirrhosis. In some cases it
can also be an asymptomatic carrier condition. There are no preventative vaccines or
effective treatments currently so universal precautions and adequate screening of the
blood supply are essential.
Hepatitis D or HDV or delta virus;
This is an incomplete RNA virus and is unable to replicate or infect very effectively except
in the presence of HBV. HDV is transmitted via the blood and it will increase the severity of
an HBV infection.
Hepatitis E or HEV ;
This virus is a single stranded RNA virus which creates s/s similar to HAV and like HAV it
is fecal-orally transmitted. Typically you see a severe though self limiting acute infection. It
is more common in Asia and Africa and it can cause significant mortality, especially to
pregnant women.
Generally for Acute viral hepatitis infections there are several distinct stages to the course
of the infection including;
The pre-icteric stage or prodromal stage. Which can be very vague and generalized
involving few symptoms or things like fatigue, malaise, nausea and muscle aches like
many other viral infections. There may be some URQ discomfort d/t livefr enlargement
and elelvated blood levels of intracellular hepatic enzymes ( eg. ALT, AST etc.).
The icteric stage involves jaundice ( elevated blood levels of bilirubin as seen as yellowish
colouration in skin and connective tissues . There may be a wide variety of manifestations
of decreased liver function such as prolonged clotting time, pale stools, dark urine, pruritis,
wider variations in blood chemistry and endocrine imbalances as well as hepatomegaly
and ||URQ| pain.
The post-icteric stage or recovery stage may last for weeks and show gradually reducing
s/s .
Alcohol abuse and alcohol liver disease:
Several important aspects of alcohol need to be understood;
it is extremely toxic- no living cells can tolerate exposure to it for very long without dying.
That is why the liver is so well adapted to detoxifying this chemical
Alcohol is lipid soluble and so it is rapidly absorbed along the entire length of the digestive
tube from mouth to large intestine. It also is able to rapidly cross the blood brain barrier
that protects us against so many other toxins.
Alcohol has an extremely high energy content.. Much higher than CHO’s it delivers about
75% more calories by weight than carbohydrates. A single serving of alcohol is about as
many calories as eating a whole potato but it also has no nutrient content.
The brain can normally only use glucose as an energy source but since alcohol can be
quickly metabolized into acetyl CoA the brain can utilize it as well. In fact because of its
high energy content the brain will preferentially use alcohol as an energy source and so we
can develop neurological dependence.
As dependence increases there is a risk that when alcohol is not available the brain will
undergo a withdrawal response. This can be a very serious problems for those addicted to
alcohol because the withdrawal symptoms can include; tremors, Delirium tremens,
hallucinations, a variety of psychoses and seizures.
Alcohol acts as a neurodepressant - similar to barbituates and other pharmaceuticals so it
may exacerbate their effects and , of course, decrease many brain functions
Since alcohol is so toxic the liver has adapted by having two different systems for
detoxifying it;
A. Alcohol dehydrogenase enzyme found in the hepatocytes cytoplasm.
B. MEOS or Microsomal Ethanol Oxidation System – and array of enzymes that
participate in the detox of many chemicals. MEOS is found in the smooth endoplasmic
reticulum of hepatocytes.
For both systems increasing levels of alcohol intake will provoke an increase in the
production of the enzymes for detox. This will lead to the development of tolerance. Heavy
drinkers are able to consume more alcohol and not show the toxic inebriating qualities as
quickly because they are detoxifying the alcohol more quickly. Drunkenness becomes
much more expensive to achieve ( bizarre a goal as that may be) but more importantly this
increase in detox enzyme levels will interfere with pharmaceutical drug actions. Many
pharmaceuticals are broken down by the same enzyme systems as alcohol and this has
two important implications. If an alcohol abuser is not drinking then the enzymes are
available for detox of other drugs so in order to maintain an adequately therapeutic
circulating level of the drug a much larger dose must be taken. Often dosages far higher
than typical are require. If, however, the individual begins drinking alcohol again then the
alcohol competes with the pharmaceutical for detox enzymes and so even a low dose of
the drug may lead to toxic overdose blood levels. For this reason few practitioners are
willing to prescribe a high dose of a drug to treat other health issues because of the risk of
overdose. The competitive effect of alcohol for the detox enzymes also can lead to
toxicities for a variety of industrial solvents, carcinogens ( eg. Aflatoxins and nitrosamines)
vitamins( mainly A & D ) anesthetics and some simple over the counter drugs such as
acetaminophen),.
Alcohol abuse, of course, has many other negative effects including;
interference with the liver metabolism of uric acid leading to uric acid accumulation. This is
referred to as gout and it can be very painful as uric acid crystals accumulate in tissues
such as the joints.
Direct damage to the GI mucosa leading to high risk of peptic ulcers and pancreatitis
Malnutrition as a result of a decrease in food intake since alcohol can meet the bodies
requirement for energy ( high caloric content) and so an individual can feel satiated and
not seek food intake. Alcohol though has no nutrient content so general malnutrition
develops and this can often be observed as tissue wasting. Often the muscles of the arms
and legs decrease significantly in mass.
Since the liver is the site of alcohol detoxification – prolonged exposure of the liver to
alcohol can lead to direct damage to liver tissue. Initially the liver is able to cope with cell
loss caused by ethanol toxicity because it has a limited ability to regenerate. New cells
grow back to replace those that are killed. Eventually ,though, alcohol damage will exceed
the ability to regenerate and so the necrotic tissue is replaced by fibrous connective tissue
or scar. This replacement of normal ( parenchyma) tissue with scar is referred to as
cirrhosis . Scar has two disadvantages.
Scar only fills in spaces where tissue damage has occurred and it is unable to carry out the
functions of normal tissue such as hepatocytes and so we see many of the same s/s as
with other forms of hepatitis/hepatocellular jaundice. Blood chemistry varies more widely –
including [glucose] and amino acid profile. Blood hormone levels are more variable and
often reach much higher levels ( eg. Gynecomastia, amenorrhea, hirsutism, Cushings
syndrome etc.). Many metabolic byproduct levels rise to toxic status, unconjugated
bilirubin levels rise and bile production is reduced. The levels of blood proteins produced
by the liver are also reduced – including complement, clotting proteins , transport globulins
and albumins. The second disadvantage to scar is that it is a much more disorganized
tissue so that the normal sinus channels of the liver through which blood from the
splanchnic circulation percolates from the hepatic portal vein to the hepatic vein become
disrupted. This slows the passage of blood through the liver and backs it up into the
splanchnic circulation ( ie. Increased hepatic portal pressure). This elevated portal
pressure can lead to varicosities ( varicose veins) in the GI circulation- especially it can
cause esophageal varicies that can gradually erode away and lead to massive bleeding
into the gut. This can lead to hypovolemic shock d/t blood loss and azotemia as a result of
rapid digestion of all those blood proteins in the gut. Azotemia is neurotoxic in its effects
and can lead to coma..
Abdominal ascites and edema are also common as a result of the increased local
venous hydrostatic pressure ( ie. Increased portal pressure) and also because the
compromised liver is no longer producing adequate albumins so that the blood Osmotic
pressure is reduced.
Before alcohol causes cirrhosis there are a number of alcohol-induced changes in the
liver. Initially the liver is provoked into greater lipogenesis and the fat is accumulated in the
hepatocytes and the liver enlarges and becomes yellowish in colour. This condition is
referred to as Fatty Liver Disease. It can be reversed if an individual ceases to ingest large
amounts of alcohol but it is also the first step to cirrhosis if alcohol abuse is not
discontinued. Alcoholic hepatitis is an intermediate stage that will follow fatty liver disease
is alcohol consumption continues. The s/s can be similar to those of other forms of
hepatitis – including jaundice, hepatomegaly, s/s of reduced liver function etc but if there is
very high levels of alcohol intake it can also become dramatically and rapidly fatal. In many
cases – because of the regenerative capacity of the liver – if drinking is discontinued the
condition can resolve. If not it can progress to cirrhosis.
Appendicitis:
This is a common problem affecting 7- 12 % of the population at some point. It can occur
at any age but it is most common in the age 5-30 range – especially for 20-30 year olds. It
involves obstruction inflammation and infection of the appendix ( a narrow blind tube at the
junction of the ileum and the large intestine- a evolutionarily vestigial organ with no
function in humans so the typical treatment involves surgical involvement with typically no
complications. Obstruction may be d/t fecoliths, scar tissure, twisting (eg.volvulus)
andforeign bodies such as buttons, plastic, fruit pits, coins etc. This leads to stasis of
secretions/contents leading to irritation that results in inflammation. Subsequently there
can be overgrowth of bacteria the invade the wall leading to further inflammation. The
increased pressure, stretching of the wall and inflammatory mediators can lead to severe
pain and gradually erosion of the wall. The inflammation can cause local peritonitis and
there is the risk of rupture leading to severe bacterial peritonitis. The earlier peritonitis can
also lead to increased LI wall permeability leading to bacterial peritonitis.
Early s/s
-
include a sudden onset of generalized abdominal pain ( epigastric of periumbilical)
that is often wavelike or intermittent. The pain results from stretching of the
appendix wall. This severe pain can lead to anorexia, nausea ( possible vomiting)
and an SNS response.
Later s/s
-
( ie 2-12 hours later) pain becomes localized in the lower right quadrant and
becomes more steady. This is d/t local parietal peritonitis. It may be aggravated by
walking, coughing, bending or external pressure. There is often rebound tenderness
–ie area is compressed and pain reduces but returns when the pressure is
released.
Often there will also be systemic s/s including mild fever, leukocytosis, malaise and
increased ESR.
There may also be constipation or diarrhea and rigid abdomen associated with peritonitis(
spasming of abdominal muscles over the inflamed area)
Notes on first aid. It is a medical emergency(911) and no laxatives should be given(
could provoke rupture), no pain relief medication that might masks/s and no heat applied
because it could exacerbate the inflammation.
Complications include – perforation of the appendix wall ( often indicated by sudden
cessation of the pain) potentially leading to life threatening peritonitis
- gradually developing bacterial peritonitis as inflammation continues
- abdominal abscess leading to obstruction
Peritonitis. This term refers to inflammation of the peritoneum. There are two main causal
categories of peritonitis. Chemical peritonitis occurs when any caustic or irritating
substances enter the peritoneal/abdominal cavity. This can include solid materials like
surgical sponges or gauze , or instruments, suture materials etc but most commonly it is
chemicals such as blood that has leaked in or perhaps caustic materials that have entered
the cavity via gut perforations or ruptures – this can include gastic HCl or pepsin through
stomach ulcers, enteric and pancreatic enzymes through duodenal peptic ulcers, bile from
a gall bladder rupture or perforation or enzymes in pancreatitis.
The other main form of peritonitis is infection. Typically this will be gut bacteria that have
passed through into the cavity through diverticulitis or appendicitis but it can also occur if
there is chemical peritonitis that has caused peritoneal inflammation that increases the
permeability of the gut wall allowing bacteria to pass through – ie bacterial peritonitis as a
sequel to chemical peritonitis. Bacterial peritonitis can also occur as a result of abdominal
ascites or as a result of bacterial infection resulting from peritoneal/ internal dialysis.
Peritonitis may be localized leading to local severe pain etc but it may also be
generalized to much of the peritoneum./abdominal cavity. In this case the pain will be
extremely severe with an accompanying severe SNS response as well as nausea and
vomiting. It can lead to paralytic ileus or silent bowel – a form of functional obstruction
since the inflammation interferes with neural control over peristalsis and peristalsis ceases.
Peritonitis can be very difficult to treat and resolve and has a very high mortality rate
associated with it.
Intestinal Obstructions
They can be classified into two main categories
A. Mechanical (physical obstructions) including;
Adhesions- abdominal fibrosis. Scars lead to tension and constriction
Hernias- protrusions through weakened walls-> trapping and strangulation
Volvulus – twisting leading to compressed BV and nerves-> gangrene
Intussusception – proximal area invaginates into distal portion) or telescoping
Neoplasms either intrinsic (inside) or extrinsic ( compressing from outside)
Foreign bodies–gallstones, impacted feces -especially in narrowed regions of the gut
Strictures – congenital or d/t scarring in radiation therapy, Crohn's, diverticulosis
B Paralytic Ileus –cessation of peristalsis as a result of impairment of neurological control. This
can happen d/t direct irritation such as with handling in surgery, trauma etc. or with visceral
peritoneal irritation such as in peritonitis. It can also be associated with ischemic effects such as a
thrombosis or a pinched blood vessel with volvulus or intussusception. Sometimes severe
systemic effects from diseases such as pneumonia, MI or electrolyte imbalances ( eg.
hypokalemia) can also cause it.
Renal pathology
Urinary Tract Infections: or UTI’s can be classified as
Lower UTI’s are infections involving the bladder (cystitis) or urethra (urethritis) and they
are far more common than upper UTI’s. The most common causative organisms are
usually bacteria that are normal flora of the GI tract, especially Escherichia coli but
also including Klebsiella, Proteus, Enterobacter etc. Other possible causes are some
STD’s and some vaginal normal flora but they tend to be much less common.
Predisposing factors include;
1. - gender ie. much more common in females d/t their shorter urethra which is less
distance for bacteria to travel between urine flushings in order to reach the bladder.
2. - poor hygiene - it is important to reduce the bacterial population around the
urethral orifice
3. - catheterization and other invasive procedures that can introduce bacteria further
up the urethra or into the bladder
4. - other underlying pathologies like chronic renal failure or prostatitis or urinary
calculi that reduce urine flow and so decrease the flushing action
5. -Diabetes which involves reduced immunity, decreased bladder sensitivity and a
high level of glucose in urine that can support bacterial growth.
6. - some sexual practices
7. - age. The very young are at risk since they may have longer exposure to feces in
diapers, the elderly may be at risk because they may have weaker abdominal
muscles and less bladder muscle tone and so they have reduced urine flow but the
biggest age group at risk is those 15-24 probably d/t greater sexual variation/less
routinized practice
Signs and symptoms of lower UTI’s include
-
urgency, frequency, often dysuria and some lower abdominal or back discomfort. In
some cases, depending on the severity and bacterial species involved the urine
may have a cloudy appearance and have a characteristic unpleasant odour or may
be possibly tinged with blood if the bladder wall becomes too inflamed.
The main complications of lower UTI’S include increased risk of an upper UTI by moving
up the urinary tract directly, increased risk of forming urinary calculi and increased risk of
future UTI’s.
Treatment
-
generally involve antibiotics and increased fluid intake.
Prevention
-
can involve increased fluid intake, drinking cranberry juice because of its high level
of phenols and tannic acid which have an antimicrobial effect. Tea also contains
tannins and has a mild diuretic effect. Improved hygiene and altered sexual
practices ( eg. Pee right after sex) etc. can all help.
Upper UTi’s can involve the ureters and kidneys including the renal pelvis and extending
into the nephron tubules. This is referred to as pyelonephritis. The causes are typically
direct spread from a lower UTI but it is also possible to have the infection arrive via the
blood in a systemic infection. Congenital structural anomalies such as a duplex kidney (
two ureters leaving one kidney allowing reflux of urine) can also predispose.
The signs & symptoms of upper UTIs usually involve all the s/s of lower UTI’s ( if you
have an upper UTI it is unlikely that you would not have a lower UTI) plus there are
usually a number of systemic s/s such as a moderate to high fever with shaking and chills,
nausea and possibly vomiting, malaise, pain with percussion in the costa/vertebral angle
and constant flank pain as the inflamed kidney stretches the renal capsule.
Upper UTI’s can lead to complications such as Chronic renal failure as nephrons are
gradually destroyed or if there is bilateral reduction in kidney function that develops quite
quickly there could be acute renal failure.
Renal Calculi or kidney stones or urolithiasis:
Renal calculi are solid masses that precipitate out of the filtrate/urine typically in a
crystalline form. The main factors that predispose to calculus formation include;
A.) High solute concentration in the urine/filtrate. Some examples of cause include;
- high [Ca++] d’t a high calcium or vit.D diet , bone disease leading to osteoporosis,
hyperparathyroidism or immobility.
- high oxalic acid or oxalate concentration in the diet. Sources include chocolate, tea ,
cocoa or rhubarb.
- high magnesium ammonium phosphate as a result of a urinary tract infection by
bacteria- especially with alkaline urine.
- a high uric acid concentration associated with a high purine, high protein diet or with
conditions of impaired liver function leading to decreased uric acid metabolism leading
to gout symptoms. A common cause of this is alcohol abuse.
- low water concentration of the urine that automatically leads to a high [solute]. This
could be the result of a low water intake or some other form of dehydration.
B.) Surfaces to act as foci for precipitation of solids. Charged surfaces especially
stimulate precipitation of dissolved solutes. Tissue debris or scarred surfaces as a result of
infection can provide these surfaces as can the presence of previoiusly formed calculi - ie.
calculi lead to more calculi.
C. Stasis of urine. Anything that causes urine to sit around or accumulate for long will
allow the solute crystals to form more effectively. This could result from immobility (
eg. bed rest or unconsciousness), pregnancy as a result of progesterone induced
relaxation of smooth muscle leading to retention of urine/ incomplete bladder
emptying.. Obstruction of urine flow by previous calculi or infection can also do the
same.
D.) Urine pH . If the urine is consistently acidic it will increase the precipitation of uric acid
and oxalates. If it is consistently alkaline it will increase precipitation of calcium or
phosphate salts. Factors such as medications or medical infections or the use of antacids
as well as ongoing challenges to systemic acid/base balance can alter the urine pH.
Kidney stones
-
are often asymptomatic - passing through the system unnoticed. Symptoms occur
when the stones are large enough and the passageways narrow enough to lead to
abrasion or obstruction. In some locations such as the renal pelvis they can become
quite large - looking like staghorn coral - without necessarily dislodging and causing
s/s.
Some typical s/s include ;
- severe pain d/t abrasion and if the fluid accumulation leads to distension of the bladder
or pelvis ( leading to swelling of the kidney and stretching of the renal capsule).
The pain is often spasmodic or colicky pain as the smooth muscles spasm and it can be
felt as flank pain or perineal depending on the site of obstruction/abrasion. Indications of
the severity of the pain can be seen in scale of the SNS response. There is often
accompanying nausea and vomiting. Sometimes we see fresh blood ( hematuria) d/t
damage to small BV of the mucosal linings.
Complications can include;
- further kidney stone development
- UTI’s as a result of tissue damage and obstruction leading to less effective flushing
action and urine stasis.
- Acute renal failure if the back up of urine leads to filtrate HP equalling glomerular blood
HP so that no further glomerular filtration occurs.
Benign Prostate Hyperplasia :
This increase in size and change in structure of the prostate is very common in males
over 50 years of age. The enlargement or growth is usually on the medial and lateral
regions of the gland, thus causing a narrowing or restriction of the urethra and a
subsequent restriction of urine flow.
Typical manifestations include;
- hestitancy - a delay in the initiation of urine flow until the pressure is high
enough to overcome the resistance to flow
- frequency as a result of incomplete emptying of the bladder which sometimes
can lead to bladder hypertrophy and also nocturia since the bladder wasn’t
emptied before going to bed
- reduced force of the urine stream
Typically the manifestations are initially mild and at best a mild annoyance but as the
gland continues to enlarge it can lead to complications such as increased incidence
of calculus formation and an increased risk of cystitis/urethritis. If the obstruction is very
severe or complete it can lead to hydroureter ( dilation of the ureters) and possibly
renal failure
________________________________________________________________________
______
Acute Renal Failure:
Acute Renal Failure (ARF) involves a significant and rapid decline in renal function d/t
pathologic or intrinsic metabolic damage to the kidneys which will be typically lead to
oliguria (very reduced urine output) and blood chemistry changes such as azotemia (highly
elevated blood levels of nitrogenous wastes).
The causes of ARF can be classified into three categories;
A. Pre-Renal Causes; This generally means that the kidney was otherwise normal but
that it is now receiving inadequate blood flow for a wide variety of reasons including;
i.) Heart problems such as CHF or an MI
ii.) Hypovolemic shock where there is inadequate blood volume to circulate such as in the
case of severe dehydration (d/t GI losses, inadequate intake,burnsor excess diuretics) or
hemorrhage leading to excess blood loss.
iii.) Distributive shock in which case there is a normal blood volume but there is vascular
pooling such as in the case of anaphylactic shock or septic shock
iv.) Surgical/medical intervention causes such as when vessels are clamped during a
surgery or as a result of increased vascular resistance stimulated by anesthetics.
v.) Bilateral Renal Vascular Obstruction such as in the case of an abdominal aortic
aneurysm that compresses both renal arteries or perhaps bilateral thrombus obstruction.
B. Post-Renal Causes: This involves obstruction of urine outflow from the urinary tract
causing a backup into the kidneys which will raise the hydrostatic pressure of the tubular
filtrate so that it exceeds of equals the hydrostatic pressure of the glomerular capillary
blood so no net filtration can occur. This could occur d/d
i.) obstruction of the bladder outlet to the urethra by an enlarged prostate or bladder
inflammation.
ii.) urethral obstruction by the prostatitis, blockage by a urinary calculus, a tumour or
severe infection or by traumatic damage.
C. Intra-Renal Causes; that involves an initial problem with the kidneys themselves. There
are many possibilities here including;
i.) exposure to nephrotoxic chemicals which damage the nephron tubules such as
- some antibiotics reactions such as with penicillin, tetracycline, aminoglycosides
and cephalosporins
- heavy metal exposure such as to lead, mercury, arsenic or uranium
- some organic solvents such as carbon tetrachloride, ethylene glycol and
methanol (wood alcohol)
- radio-opaque contrast media such as barium used in medical diagnostic tests
- some pigments such as when there is exposure to large amounts of
haemoglobin in transfusion incompatability reactions or DIC or with exposure
to myoglobin in muscle crush injuries
ii.) acute glomerulonephritis
iii.) acute inflammatory diseases such as acute pyelonephritis ( upper UTI)
ARF initially has an oliguric phase in which there is a great decrease in urine output as
there is decreased kidney processing.
This will lead to the blood chemistry changes such as elevated BUN (blood urea nitrogen )
or SUN ( serum urea nitrogen) as nitrogenous wastes are not eliminated. When more
severe it is referred to as azotemia. There will also be elevated creatinine, potassium and
phosphorus levels as well as acidosis. (d/t decreased HCO3- reabsorption and decreased
H+ secretion by the tubules). Sometimes there are the blood chemistry changes but no
oliguria with intrarenal causes because of a decreased tubular ability to concentrate urine.
Other signs of decreased renal function will be uremia ( urine components increasing in
the blood – eg. Urea etc) as well as hypertension and edema as a result of attempted
compensation for the decreased GFR.
The diuretic phase may develop if the causes of ARF are resolved – with in a few days
or up to 6 weeks after oliguria. Generally this indicates a return to normal function or
recovery though the chemical changes persist as function recovers and the excess wastes
are gradually reduced.
ARF is often potentially reversible if it is detected and effectively treated early enough.
Treatment can include;
●
- resolving the underlying causes such as by restoring blood flow, resolving the
obstruction or removing the nephrotoxic agent.
● - maintaining fluid and electrolyte balance
● - maintaining the CHO intake but reducing protein intake to prevent protein
catabolism and reduce the risk of producing nitrogenous wastes.
● - possibly dialysis to maintain acceptable blood chemistry.
If treatment is successful then there may be no permanent damage but if not renal failure
has the potential to become rapidly fatal.
Chronic Renal Failure;
This form of renal failure is very different from ARF. It tends to be a gradually developing
insidious disease that is progressive, largely asymptomatic in the early stages and
completely irreversible, Generally you have no idea that you have it until the stage when
there is already very large scale damage and at that point there is nothing much you can
do about it except try to slow down its rate of progress. It is primarily associated with
systemic disorders such as hypertension and atherosclerosis linked to obesity, poor diets
and a sedentary lifestyle. It is also strongly associated with poorly controlled diabetes.
Chronic kidney diseases such as bilateral pyelonephritis can also lead to CRF. In typical
cases the blood supply to the kidneys is slowly reduced and there is a subsequent loss of
nephrons and as a result of that a decrease in GFR. We describe the progress of the
disease in three stages.
Stage1 : Renal Impairment or Decreased Renal Reserve
This involves up to 60 % nephron loss and GFR decreases to 40-60 % of normal.
Virtually no symptoms and the only signs are a measureable decrease in GFR and a high
normal blood creatinine level.
Stage II : Renal Insufficiency
This involves up to a 75 % nephron loss and GFR is reduced to 20 - 40 % of normal. At
this stage you see alterations in blood chemistry, Usually there is moderately elelvated
BUN (eg. elevated blood urea and creatinine) , moderate acidosis and diuresis ( d/t the
decreased ability of the remaining tubules to adequately concentrate urine). This may lead
to polyuria and nocturia. Anemia is another common symptom as a result of a decreased
kidney production of erythropoietin.
Stage III or End Stage Renal Failure
This involves a 90% nephron loss and a GFR down to 10-15 % of normal. At this point
blood chemistry changes are severe and there is a wide range of manifestations including;
- Uremia (urine in blood) d/t almost complete loss of kidney function. The breath and
sweat will have a distinctly urine-like odour in many cases. Blood levels of nitrogenous
wastes are very high at this point - referred to as azotemia and this is toxic to most
tissues.
- Elevated BP as the CVS attempts to compensate for the decreased GFR ( eg.
renin-angiotensin mechanism)_
- Nervous system effects include lethargy, stupor and potentially coma d/t azotemia
and acidosis. There is also often significant memory loss and peripheral neuropathy
leading to decreased sensation and muscle control.
CI.
The skin often becomes dry, thin and brittle, sometimes with a whitish uric acid/
urea
crystal frosting and banding of the nails. There is typically pruritis (itchiness) d/t the
effects of accumulated phosphate crystals as well as azotemia
- For the GI we often see nausea as a result of the emetic centres response to toxins in
the blood. This can lead to severe anorexia. There may also be an increase in GI
bleeding d/t a decrease in blood platelet levels.
- The red bone marrow function is suppressed (bone marrow depression) by the
azotemia and acidosis and this will lead to a decrease in production of WBC’s leading to
decreased immunity, decreased RBC’s leading to anemia and decreased platelet
production leading to bleeding disorders.
- Hypocalcemia d/t a decreased in kidney activation of vit. D leading to decreased
calcium absorption. THis can lead to decreased bone density and hyperphosphatemia
as you respond to the the low blood calcium levels by increasing parathyroid hormone
which breaks down bone and released phoshate and the decreased kidney function
leads to decreased ability to clear or eliminate the excess phosphate.
- Decreased sexual function d/t decreased libido ( azotemia and acidosis affecting the
brain) and amenorrhea d/t altered endocrine function.
At this stage increasingly frequent dialysis is required to maintain blood chemistry within
acceptable parameters but ultimately the only longterm treatment is a kidney transplant (
though there are usually long waiting lists) - otherwise the condition will lead to death.
The next two pathologies involve glomerular inflammation/disease
Acute Post Streptococcal Glomerulonephritis or APSGN - a form of Acute Nephritic
Syndrome. This pathology is most common in children especially around the age of 6-7 at
about the time that most children begin school and encounter many more children and
pathogens. It is about 2x as common in boys and typically develops at one to two weeks
after a nasopharyngitis episode caused by group A, Beta-hemolytic Sreptococcus
pneumoniae ( ie. Strept throat) as a result of a type III hypersensitivity reaction in which
antibodies are produced to certain bacterial antigens to form antigen-antibody complexes
that form an insoluable precipitate. This complex will then bind to the surfaces of
endothelial cells that form the capillaries, line larger blood vessels or the heart chambers
or even the heart valves. In APSGN they bind to the glomerular capillaries and cause
inflammation.
The inflammatory changes to the glomerulus lead to two main effects;
i. the lumen of the glomerular capilleries is narrowed and this leads to a reduction in
glomerular filtration (ie. a decreased GFR)
ii. the glomerular capillary wall becomes more permeable d/t larger gaps between
adjacent endothelial cells. This allows larger things that normally don’t filter to pass
through into the filtrate, including blood proteins and cells.
These two effects account for most of the manifestations of APSGN.
The increased glomerular permeability means that now we will see RBS’s in the urine–
hematuria – causing a dark coffee or tea like colour for the urine and there will also
protein in the urine ( proteinuria) making the urine cloudy. In addition since some of
the RBC’s and proteins will start to clog up the tubules they will consolidate and be molded
into the shape of the tubules until they are forced out under pressure leaving tiny cylinder
shaped objects in the urine known as urine casts or cylinduria.
The decreased GFR will lead to an overall decrease in urine output or oliguria and in
response to the decreased GFR the kidneys will release more renin which through the
angiotensin effects will lead to widespread peripheral vasoconstriction thus raising the
PVR and resulting in severe hypertension. The hypertension will cause and increase in
hydrostatic pressure in the systemic capillaries and this will lead to widespread moderate
systemic edema – seen especially in the face and dependent areas and with a general
weight gain d/t fluid retention in the tissues. With the decrease in kidney function there will
be significant blood chemistry changes including elevated B.U.N. or (S.U.N.) , metabolic
acidosis, elevated creatinine and also elevated levels of serum ASO ( antistreptolysin O –
an exoenzyme against Streptococcus and systemic signs of inflammation such as an
increased ESR. The individual usually also has accompanying flank pain and feels typical
symptoms such as malaise, lethargy and irritability.
The prognosis for APSGN is usually pretty good for children – about 95% recover
completely without further reoccurrence. For adults only about 60% completely recover
without any kidney damage.
Complications can include;
- CHF – as a result of the heart having to work against severe hypertension
- Encephalopathy – as a result of the hypertension leading to cerebral edema as well
as the exposure to acidosis ( a neurodepressant) and moderate azotemia ( high
levels of nitrogenous wastes in the blood)
- ARF if there is continued severely decreased GFR and larger scale damage to
tubules. If only slowly resolved and with longer term but more gradual tubular
necrosis it could lead to CRF.
Nephrotic Syndrome or Nephrosis
This is another glomerular pathology that involves glomerular inflammation that develops
in a different way. It can have many causes and so it can be thought of as a glomerular
manifestation of a variety of pathologies.
The most common form of nephrosis in children is called Minimal Change Nephrotic
Syndrome – a primary form of nephrosis. It is seen mainly in preschool age children, 2-7
years old with a peak occurrence in 2-3 year olds. It is more common in males than
females and accounts for about 80% of nephrosis in children.
Predisposing factors include
-
a preceeding viral URI and in some cases a familial ( maybe genetic) factor.
Treatment
-
This form of nephrosis if treated quickly and effectively (eg. Corticosteroids mainly)
typically resolves completely with little or no permanent damage though it has a
tendency to recur.
Secondary nephrosis can occur secondary to a variety of pathologies including Acute
glomerulonephritis, SLE, drug toxicities, insect stings and other animal venoms, sickle cell
disease , malaria, diabetes or Tuberculosis.
In nephrotic syndrome the inflammatory change in the glomerulus is a little different leading to a
greater loss of proteins but usually no loss of RBC’s so we see no hematuria but often much larger
loss of blood proteins – gross proteinuria. Especially high levels of albumins are lost in the urine –
gross albuminuria and this loss leads to hypoalbuminemia. We also see casts in this pathology but
the cylinduria are composed mainly of proteins ( no RBC’s).
The severe loss of albumins leads to a major decrease in systemic blood Osmotic pressure and so
this leads to severe systemic edema ( much worse than APSGN) and as a result of the fluid shift
from blood to ISF there is a decrease in blood volume so we don’t see hypertension in spite of the
renal response to decreased GFR. This low OP can also lead to severe ascites, pleural effusion and
elelvated ICP.
Another unusual finding is hyperlipidemia and lipiduria probably as a result of a generalized liver
response to having to gear up to replace the albumins that have been lost.
General manifestations then include oliguria, gross edema, significant weight gain (increased fluid
retention in tisues), dyspnea (d/t pleural effusion), diarrhea (d/t GI edema) and CNS depression.
Complications can include, among other things, a decrease in immunity and a resulting increased
risk of infection d/t the immune suppressing effects of the corticosteroid treatment, the loss of
complement and gamma globulins in proteinuria and the effects of edema in decreasing exchange
and nutrient delivery to tissues.
With aggressive treatment there is usually recovery within 7-21 days though there is a high risk of
relapse in many (around 50% ) cases.
Renal anatomy
-
The renal papilla is the location where the meduallary pyramids empty urine into cuplike
structures called minor and major calyces
The minor then major calyces receives urine from the papilla of one renal pyramid
Once the filtrate centers the calyces, it becomes urine because no further reabsorption can
occur
In the kidney the renal papilla is the location where the medullary pyramid empty
urine into the renal pelvis. Histologically it is marked by medullary collecting ducts
converging to channel the fluid. Transitional epithelium begins to be seen
Structures of the kidney
Functions of the nephron
-
To produce urine, nephrons and collecting ducts perfrom three basic processes;
glomerualr filtration, tubular reabsorption, and tubular secretion
- Glomerualr filtration: is the first step of urine production -blood pressure forces
water and most solutes in blood plasma across the wall of glomerualr capillaries
- Tubular reabsorption: returning most of the filtered water and many of the filtered
solutes to the blood, is the second basic fucntion of the nephrons and collecting
ducts
- Tubular secretion: the tubule and duct remove substance, such as wastes, drugs
and excess ions, from blood in the perilubular capillaries and transport them into the
fluid in the renal tubules.
Cortical nephron
Function of the nephron
Filtration, reabsorption, and secretion in the nephron and collecting ducts
Functions of the nephron
- Epithelial cells all along the renal tubules and collecting ducts carry out tubular
reabsorption and tubular secretion. Tubular reabsorption retains substances
needed by the body, including water, glucose, amino acids, and ions.
- Angiotensin II enhances reabsortion of Na+ and Cl-. angiotension II also
stimulates the adrenal cortex to release aldostrone, which stimulates the collecting
facts to reabsrob more Na and Cl and secrete more K. atrial natriuretic peptide (
ANP) inhibits reabsorption of Na ( and Cl and water) by the renal tubules, which
reduces blood volume.
- The major hromone that regualtes water revaorptin is antidiuretic hromen ( ADH),
via negative feedback.
Transportation, storage and elimination of urine
-
Urine produced by the nephrons drains into the minor calyces, which join to
become major calyces that unite to form the renal pelvis
From the renal pelvis, urine drains first into the ureters and then into the urinary
bladder; urine is then dischraged from the body through the urethra
The two ureters transport urine from the renal pelves of the right and left kidneys to
the urinary bladder
The wall of the ureters conistss of 3 layers; transitional epithelium on the inside (
mucosa), smooth muscle in the middle, and an outer layer of areolar connective
tissue
The urinary bladder is aholow muscualr organ in the pelvic cavity posterior to the
pubic symphysis. Its fucntion is to store urine prior to micturition
The mucosa of the urinary bladder contains transitional epithelium and rugae. The
muscular layer of the wall consists of three layers of smooth muscle called the
detrusor muscle. The outer coat is a fibrous covering.
Urine produced by the nephrons drains into the monor calyces, which join to
become major calyces that unite to from the renal pelvis.
-
-
Blood
disorder
From the renal pelvis, urine drains first into the ureters and then into the urinary
bladder; urine is then discharged from the body through the urethra
The two ureters transport urine from the renal pelves of the right and left kidney to
the urinary bladder
The urthera, the terminal portion of the urinary system, is a small tube leading from
the floor of the urinary bladder to the exterior of the body. In females, it lies directly
behind the pubic symphysis and is embeded in the front wall of the vagina, between
the clitrois and vaginal opening. In males, the urethra passes vertically through the
prostate, the deep perineal muscles, and finally the penis
The micturtion reflex discharges urine from the urinary bladder by means of
contraction of the detrusor muscle and relaxation of the internal urethral sphincter
muscle, and by inhibtion of the external urethral pshincter
Anemias
- There are two general causes of anemias they are:
- A. excess loss of RBC’s d/t excess bleeding losses or excess RBC destruction
- B. insufficient production of RBC’s d/t factors such as nutritional deficiencies or
bone marrow depression
Increases hemopoiesis is generally insufficient to compensate for either of the two
general causes. In the case of insufficient production there is no opportunity for
erythropoiesis since the capacity to do so has been lost ( eg, nutritional deficiency).
In the case of excess loss of RBC’s the rate of loss is much greater than the rate of
replacement
Basically: the main problem of anemia is that insufficient oxygen is being delivered
to tissues. This will cause many effects including:
● An increase in heart rate and strength of contraction in an attempt at
compensation. Chemoreceptors will detect low blood O2 concentration and
stimulates the meduallryCVC centre to stimulate the heart. Over time this can
lead to ventricular hypertrophy.
● Pallour ( pale color ) of the skin, mucosa and nail beds in part because of the
reduction in hemoglobin pigment ( red pigment) and partly d/t SNS stimulated
peripheral vasoconstriction in an attempt to increase BP in order to increase
blood flow to tissues
● The rate and depth of breathing will be increased d/t the stimulation of the
RCC in the medulla by chemoreceptors that have detected the low blood (
O2)
● CNS fucntion will decreased d/t the hypoxia. This will in dizziness and
fainting and decreased neural activity generally
● Exercise intolerance will develop d/t the decreased delivery of o2 to muscle
and neurons. The individual will fatigue easily and feel weak
● The rate of cell regeneration for healing /repair will decline d/t hypoxia
● The reproductive system will be affected in several ways. Decreased oxygen
delivery will lead to decreased gametogenesis ( esp. In males) leading to
decreased fertility. In females amenorrhea is a common outcome and in both
genders the decreased in oxygen delivery to the brain can lead to loss of
libido
➔ Anemia that develops rapidly to severe levels may show immediate s/s that result
from:
➔ i) the effects of hypoxia eg. fatigue weakness, angina, headaches and dizziness
➔ ii) the effects of the compensation eg. tachycardia and pallour and increased resp
rate
Other s/s may arise depending on the cause of the anemia. For example excessive
destruction of RBC’s may lead to jaundice ( yellowish coloration of the skin and sclera d/t
accumulation of bilirubin produced by hemoglobin breakdown.
If the anemia develops more slowly there may not initially be any obvious s/s because
since the body is bale to gradually adapt through compensatory mechanism. Cardiac
output may increase red bone marrow may be stimualte to try and increase RBC
production and the hemoglobin may be altered to increase its ability to release more O2 to
the tissues ( eg, hemoglobin affinity for O2 is reduced)
Severe chronic anemia may lead to angina pain as the heart muscle works harder but
receives less oxygen. Gradually to adapt to the increased workload the ventricles may
hypertrophy which of course means that the cardiac muscles will need even more O2. this
can lead to angina and ultimately to heart failure. Other problems could include a
decreased growth of tissue ( especially epithelial tissue)
Some of the common type of anemia, classified based on cause, include:
IRON DEFICIENCY ANEMAIA.
ESSENTAILLY this from of anemia is the result of there being inadequate iron available for
the synthesis of hemoglobin