Pathophysiology pearls Flashcards
DIC
Complement activation pathways and cascade
Diagnosis of chylothorax and chylous ascites
Milky fluid
Presence of chylomicrons
Triglygeride greater than 2mmol/L (and often >10mmol/L)
Nutrition screening tool
MUST screening tool, 5 step process
- Obtain BMI
- >20=0, 18.5-20=1, <18.5=2
- Percentage of unplanned weight loss
- <5=0, 5-10=1, >10=2
- Disease effect
- acute illness AND has been or likely to be poor intake >5 days
- Calculate score
- 0 low risk
- 1 medium risk- observe intake 3/7
- 2 high risk- needs intervention
- Make and undertake a plan
What is the Fearon- Vogelstien model?
Grading and parameters of haemorrhagic shock
What is an MTP
What are the constituents
What monitoring is recommended
A system designed to rapidly replace blood products at an approximate 1:1:1 ratio in a patient who is exsanguinating.
- The exact protocol differs between centres
At our centre the MTP is activated by a clinician who thinks it is warranted.
- Additional markers for triggering the MTP include:
- loss of half of estimated blood volume,
- use of 10 packed red cell units, or
- a score of 2 or more in the ABC trauma score
- 1 point each for penetrating trauma, HR >100, SBP <90, or positive FAST
Our protocol is:
- The first box contains
- 2 units of RCC and 2 units of FFP
- The second box contains
- 4U RCC + 4U FFP + 3U cryoprecipitate
- The third box contains
- 4U RCC + 4U FFP + 1U platelets
- Box Four is the same as the second box and these keep rotating.
The patient should receive 1g of TXA on arrival
The patient’s coagulation status should be continuously monitored with TEG, ROTEM, or coags as well as calcium and an ABG
Some centres use recombinant VIIa, although this is not widespread practice.
ABC trauma score
1 point each for:
- Penetrating trauma
- HR >100
- SBP <90
- Positive FAST
A score of 2 or more is an indication to commence the MTP
PTEN
Tumour suppressor gene
- Regulates cell cycle
- Widely expressed in most tissues
Associated conditions
- Cowden syndrome/Cowden-like syndrome
- Breast cancer (at least partly Cowden)
- Lung cancer
- Prostate cancer
- Head and neck SCC
- Thyroid Cancer
- Esp follicular cancer
Cowden syndrome and Cowden-like syndrome
Autosomal dominant
These conditions are characterized by the growth of multiple hamartomas and cancers,
- Lipomas, papillomas
- Breast cancer
- Thyroid cancer (follicular)
- Endometrial cancer
Cowden syndrome and Cowden-like syndrome are considered to be part of PTEN hamartoma tumor syndrome
Li-Fraumeni Syndrome
TP53 tumour suppressor gene mutation
Risk of malignancy developing in childhood and early adulthood
- lifetime malignancy risk of ~100%
- Some studies have used annual whole body MRI for surveillance which is effective but trade off with high rates of incidenatalomas
Autosomal dominant
Classical cancers
- Breast (lifetime risk 50%)
- Soft tissue and bone sarcomas (but not Ewings)
- Brain tumours
- Adrenocortical carcinomas
Less common cancers:
- Leukemias
- Adrenocortical carcinoma
- Pancreatic
- Bowel
- Many others
High association with radiation induced malignancies-
- Avoid RTx where possible
Pathognomonic histology:
“Leaf like stroma”
Phyllodes tumour
Pathognomonic histology:
“Orphan Annie Eyes”
Papillary Thyroid Cancer
Pathognomonic histology:
Psammoma body
Arise from papillary infaction and calcification in papillary forms of cancer
- Thyroid
- Papillary thyroid cancer
- Pancreas
- Somatostatinoma
- Glucagonoma
- Kidney
- Papillary RCC
- Gynae
- Ovarian and endometrial cancer
What are the phases of wound healing
- Haemostasis
- Inflammation
- Proliferation
- Maturation
These phases overlap significantly
VINDICATE
Vascular
Infectious/inflammatory
Neoplastic
Degenerative
Iatrogenic/Intoxication
Congenital
Autoimmune
Trauma
Endocrine/Metabolic
How to compose an answer to a question you do not have the answer for
In A Surgeons Gown Physicians May Make Some Progress
Incidence
Age
Sex
Geography
Pathogenesis/Precipitation
Macroscopic features
Microscopic features
Spread
Prognosis
The two hit model of tumourigenesis
First hit
- Inherited germ line mutation in a gene which would otherwise suppress malignancy
Second hit
- Sporadic mutation in the remaining functional copy of that gene in a single cell
- Clonal expansion and tumour development
Peutz-Jeghers
GI hamartoma syndrome
STK11 mutation (aka LKB1)
Pigmented mucosal lesions
Panenteric hamartomas
Very elevated risks for gastrointestinal cancers:
- Colorectal
- Stomach
- Small intestine
- Pancreas
Also breast and ovarian cancers
- Recommend increased/early surveilllance for these cancers
Hereditary diffuse gastric cancer syndrome
Germline cadherin 1 gene mutation (CDH1)
Susceptibility to diffuse, highly invasive gastric cancer
- also called:
- signet ring carcinoma
- isolated cell-type carcinoma
Also Lobular breast cancer
- Some pathogenic types this may be as high as 50%
- Generally risk reducing mastectomy not warranted unless strong family history to suggest a breast cancer pathogenic variant
PALB2
Partner and localizer of BRCA2 (PALB2)
- breast cancer susceptibility gene that encodes a BRCA2-interacting protein
- monoallelic PALB2 pathogenic variant have a risk of breast cancer by age 70 of 33 to 58% depending on family history
- the upper risk range can overlap with BRCA2 risks,
- PALB2 is considered to be a moderate to high-risk gene associated with hereditary breast cancer
- initiate annual mammography with tomography and annual breast MRI, starting at age 30 years.
- RRM may be an appropriate option for some patients
- Other cancers
- Pancreatic
- prostate cancer
- medulloblastoma
- ovarian
Tools used in recognising sepsis:
SIRS criteria
Not specific for sepsis but helpful in recognising the unwell patient
Four parameters
- Pulse
- >90
- <50
- Temp
- >38
- <35
- WCC
- >12
- <4
- Resp rate
- >20
- <8
Tools used in recognising sepsis:
qSOFA
Quick Sepsis Organ Failure Assessment
Three parameters scored 0-1
- Score of 2 or more is associated with worse outcomes including mortality and is advised by several expect panels
- It really just shows shock though and no surprises that this correlates with death in sepsis
- Parameters are:
- Respiratory rate ≥22/minute
- Altered mentation
- Systolic blood pressure ≤100 mmHg
Tools used in recognising sepsis:
EWS
Should be routine practice as they are validated.
Ki67
Antigen KI-67 is a nuclear protein that is associated with, and may be necessary for cellular proliferation.
- Immunohistochemical staining can be used to detect Ki67
- Provides information on cellular proliferation rate
Calcium homeostasis
Vitamin D synthesis and activation
Vitamin D synthesised in skin and absorbed from diet
- hydroxylated at 25 position in liver
- hydroxylated at 1 postion in kidney
- 1,25 hydroxyvitamin D3 is the active form
- hydroxylated at 1 postion in kidney
Calcium homeostasis diagram
What are the functions of calcium
Hormone secretion
Muscle contraction
Synaptic function
Coagulation cascade
PTH:
synthesis
half life
feedback
Synthesis in parathyroid chief cells
Half life of 4.5 minutes
Feedback is by ionized calcium by negative feedback
How can the causes of hyperparathyroidism be differentiated
Hyperparathyroidism is the third most common endocrine disorder after DM and thyroid disorders
Primary
- most common cause of hypercalcaemia
- autonomous function of one or more of the glands
- a new calcium set point is created
- 85% have single adenoma
- 13% have multiple gland dysfunction
- MEN1- all glands
- MEN2A- multiple but asymmetrical
- 2% carcinoma (very high Ca levels)
Secondary
- physiological secretion of PTH due to low calcium
- usually due to vitamin D defiency in the context of renal failure
Tertiary
- advanced form of secondary hyperparathyroidism
- four gland hypertrophy and autonomous functioning
- life threatening
- usually have elevated Ca and normal PTH levels
- life threatening
- four gland hypertrophy and autonomous functioning
Symptoms of hypercalcaemia
Stones
- Renal stones
Moans
- Abdominal pain
Groans
- Constipation
Bones
- Osteopaenia
Psychiatric undertones
- depression, fatigue
Define morbid obesity
BMI >35 with comorbidity
or
BMI >40
NF1
Also known as von Recklinghausen syndrome
NF1 gene 17q11
Manifestations
- Neurofibromas
- Cafe au Lait spots
- Phaeochromocytoma
Von Hippel-Lindau disease
3p25
Manifestations
- pancreatic neuroendocrine tumours (non functional)
- Phaeochromocytoma
- RCC
- Retinal and cerebellar haemangioblastomas
What are the fat soluble vitamins
A
D
E
K
Describe the physiology of B12 absorption
Intrinsic factor secreted by gastric parietal cells
- cobalamin contains B12 and is released from substrate by enzymatic degradation in the duodenum and bound to intrinsic factor
- The cobalamin-intrinsic factor complex is absorbed in the distal ileum
- B12 is freed by transcobalamin II in terminal ileal enterocytes.
- The cobalamin-intrinsic factor complex is absorbed in the distal ileum
List the causes of bowel obstruction
Luminal
- bezoar
- gallstone
- enterolith
- foreign body
Mural
- tumours
Extramural
- adhesions
- hernias
- carcinomatosis
- abscesses
Virchows triad
Virchow’s triad describes the three broad categories of factors that are thought to contribute to thrombosis.
- Hypercoagulability
- Haemodynamic changes
- stasis, turbulence
- Endothelial injury/dysfunction
What is the role of secretory IgA in the gut
Does not opsonise or activate compliment
Prevents bacterial adherence to endothelium
- prevents colonisation and multiplication
Neutralises bacterial toxins
ALARM symptoms
Weight loss
Haematemesis
Melaena
Anaemia
Dysphagia
Odynophagia
Severe symptoms
B symptoms
why are they called B symptoms
B symptoms are:
- fever
- >38
- drenching sweats
- especially night sweats
- weight loss
- >10% over 6/12
They are called B symptoms as per the Ann Arber staging system (A without and B with systemic symptoms
- associated with systemic rather than local disease
- denote a poorer prognosis
CDH1
E cadherin gene
- Rare autosomal dominant disorder
- Marked increase in diffuse type gastric cancer and breast cancer
- life time risks
- women
- 50% life time risk of gastric cancer
- 40% lifetime risk of breast cancer
- men
- 56% lifetime risk of gastric cancer
- Breast cancer risk not well defined
- women
- median age of gastric cancer age 38
- risk reducing strategies including surgery for both are reasonable
- gastrectomy generally between 20-30 years of age
- life time risks
What score can be used on histology to assess the risk of malignancy in phaeochromocytoma
The PASS score
- uses histological features e.g tumour necrosis, spindling, invasion etc to estimate risk of malignancy
- there is no perfect score for phaeochromocytoma and the only definative diagnosis can be made if a metastasis occurs
s100 histology staining
Marker of schwann cells and melanocytes
- useful for evaluating nerve sheath tumors and melanoma
What classification may be used to assess perioperative risk in cirrhosis
- What are the parameters of the score
- how is each parameter scored
- what is the interpretation of the scores
- what is the perioperative mortality by class
Child-Pugh score (this is a modification if the Child-Turcott score and includes INR rather than nutritional status- it is sometimes ereferred to as the Child-Turcott-Pugh score)
- the score has been validated as a predictive tool for mortality in performing non-shunt abdominal surgery in cirrhosis
- each parameter is scored 1-3 points
-
Albumin
- >35
- 28-35
- <28
-
Bilirubin
- <34
- 34-51
- >51
-
Coagulation (INR)
- < 1.7
- 1.7-2.2
- >2.2
-
Distension (ascites)
- absent
- slight
- moderate
-
Encephalopathy
- absent
- grade 1-2 (mild)
- grade 3-4 (somnolent/disorientated to comatose)
-
Albumin
- the system is thus scored 5-15 points
- Class A = 5-6 points
- Class B = 7-9 points
- Class C = 10+ points
- the mortality by class is
- A = 10%
- B = 30%
- C = 82%
What is the points interpretation for the Child-Pugh score
Class A = 5-6 points
Class B = 7-9 points
Class C = 10+ points
How is albumin level scored in the Child-Pugh score
1-3 points as is each parameter
- >35
- 28-35
- <28
How is bilirubin level scored in the Child- Pugh score
1-3 points as is each parameter
- <34
- 34-51
- >51
How is coagulation scored in the Child-Pugh score
1-3 points as is each parameter
- < 1.7
- 1.7-2.2
- >2.2
How is ascites scored in the Child-Pugh score
1-3 points as is each parameter
- absent
- slight
- moderate
How is encephalopathy scored in the Child- Pugh score
1-3 points as is each parameter
- absent
- grade 1-2 (mild)
- grade 3-4 (somnolent/disorientated to comatose)
What score may be used to predict 3 month mortality in cirrhosis and is frequently used for transplant prioritisation
- What are the parameters
The New MELD score
- initially developed to predict post TIPS mortality
- validated as a general model for end stage liver disease
- revised in 2016 to include sodium level as a standard variable
- Parameters are graded as continuous variables
- Sodium
- Creatinine
- INR
- Bilirubin
What pathway is implicated in intestinal type gastric cancer development
The Correa hypothesis
- Progression from atrophic gastritis
- through low grade dysplasia to high grade dysplasia and then malignancy
What are the phases of clot formation
This is a chain of events
- initial local vasoconstriction
- vWF and tissue factor exposure
- platelets activation and adherance
- activation of the coagulation cascade
- formation of fibrin from fibringen for clot stabilasation
- clot maturation and remodelling under the effects of antithrombin III and thrombomodulin
