Seminar 7 - Endocrine Disease and Its Complications Flashcards
Which tests can be done to identify the specific type of diabetes
Often T1 is diagnosed on Hx and PC alone (e.g., DKA)
If in doubt, GAD/IA2 antibodies [and c-peptide] may help
What is Cushing’s syndrome
A disease resulting from chronic excess of glucocorticoids
Why is endometrial cancer often diagnosed early
Post-menopausal bleeding is a common symptom which many women know to have checked so it often leads to early detection and good prognosis.
Which differentials must you consider when diagnosing osteoporosis
Metastatic bone malignancy
Osteomalacia – Difficult to differentiate clinically
Multiple myeloma – Symptoms include bone pain as well as those of anaemia and renal failure
Cervical cancer can affect your sex life - true or false
True
Can be due to treatment side effects or psychological/emotional
Also cannot have vaginal sex for a time after surgery
What is the precursor lesion for serous endometrial carcinoma
Endometrial intraepithelial carcinoma.
What determines the outcome of breast cancer
The stage at presentation
Biological features - e.g. whether it is ER, HER2 of triple neg
Histological type
Which type of adjuvant therapies are available for breast cancer
Chemotherapy
Biological therapies - trastuzumab/Herceptin
Endocrine therapies - tamoxifen
List the macroscopic features of osteoporosis
Trabecular bone is most noticeably affected, but there may also be thinning of the cortical bone
Flattening of vertebral bodies
Will also find artefacts of previous fractures e.g. hip prothesis
What is hyperosmolar hyperglycaemia syndrome
Hypovolaemia and hyperglycaemia without significant acidosis or ketonemia (non-ketotic state)
Also hyperosmolar.
List symptoms that may be seen in advanced stage endometrial cancer
Patients may experience: pain in the back, legs or pelvis, loss of appetite, tiredness and nausea
In which age group is secondary systemic hypertension more common
More common in younger persons, with a prevalence close to 30% in those 18 to 40 years of age with hypertension
List the pathological features of Cervical adenocarcinoma
Characterised by proliferation of glandular epithelium composed of malignant endocervical cells.
These cells have large hyperchromatic nuclei (darker appearance) and relatively mucin depleted cytoplasm.
Describe the epidemiology of cervical cancer
4th most common cancer in women worldwide.
570,000 new cases in 2018 of which more than 50% will be fatal.
50 years ago, it was the leading cause of cancer death in women.
Death rate decreased by 75%
In the UK, less than 1% of those with a cervix will develop cervical cancer in their lifetime
What is insulitis
The leukocytic infiltrates in islets seen in T1DM
Contributes to destruction of the islets
Diffuse thickening of the basement membrane underlies the development of which diabetic complications
Diabetic nephropathy, retinopathy and some forms of neuropathy
Development of end-stage renal disease is more common in which type of diabetes
Type 1
ESRD occurs in >75% of T1 diabetics (vs. 40% T2) within 20 years of developing nephropathy.
List cardiovascular causes of secondary systemic hypertension
Coarctation of the aorta Polyarteritis nodosa Increased intravascular volume Increased cardiac output Rigidity of the aorta
Which symptoms of diabetes are caused by the lack of anabolic action from insulin
Results in catabolic effects so you get:
Increased appetite
Weight loss
Muscle weakness
How does angiotensin II stimulate aldosterone secretion
It sodium resorption via Na+/K+ pump activity at basolateral membrane in the distal convoluted tubules which increases blood volume
This increase in BV triggers aldosterone secretion from the adrenal glands
What is happening to the global prevalence of diabetes
It is rising
rose from 108 million (1980) to 422 million (8.5%; 2014
List the microscopic features of serous endometrial carcinomas
Can have a papillary growth pattern or even be predominately glandular in growth pattern.
Glandular pattern can be differentiated form the similar endometroid tumours by the cytologic features.
Marked cytologic atypia including; high nucleus: cytoplasm ratio, atypical mitotic figures, hyperchromasia and prominent nucleoli.
In which ethnic groups is breast cancer most common
Risk is highest for European women
4-7x greater risk than rest of population
What are the 3 main groups of breast cancer and how are they grouped
Grouped by protein expression
HER2+ – positive for HER2 and +/- for ER
Triple negative – negative for ER, HER2 and PR
Luminal – ER + and HER2 negative
List the pathological features of Cervical squamous cell carcinoma
Composed of nests or tongues of malignant epithelium.
Can be keratinising or non keratinising.
These nests can invade the underlying cervical stroma.
List complications of testicular cancer metastasis
Lung – haemorrhage and blockage of clearance which lead to potential infection, sepsis or respiratory failure
Liver – if severe enough may reduce liver function and lead to liver failure
Brain – has the potential to bleed, cause seizures and raise the ICP
Premature birth or miscarriage due to cervical excision surgery is common -true or false
False
It is rare - only occurs in 2% of women who have had the procedure
How do Selective Oestrogen Receptor Modulator (SERM) work in osteoporosis
Only appears effective in reducing vertebral fractures
How can you differentiate well differentiated endometroid endometrial carcinoma from endometrial hyperplasia
Can be differentiated from hyperplasia by presence of complex growth patterns (e.g. papillary) or desmoplastic stroma
In which % of secondary hypertension patients have Cushing’s
~80% of adult patients
~47% in children
What additional risks need to be addressed in DKA
Is a NG tube required?
Monitor K+
Prescribe LMWH
Source sepsis if present: CXR, cultures
Does diabetic neuropathy mainly effect sensory or motor neurons
Sensory
Which medications can increase the risk of cervical cancer
Oral contraceptives
Increase risk in those already infected with HPV
How does the brain regulate food intake
BY responding to signals received from fat (adipose) tissue, the pancreas, and the digestive tract
These signals are transmitted by hormones—such as leptin, insulin, and ghrelin—and other small molecules (controlled by genes)
The brain coordinates these signals with other inputs and responds with instructions to the body: either to eat more and reduce energy use, or to do the opposite
Which hormones are commonly released by Leydig cell tumours
Cells commonly release androgens, estrogen and corticosteroids
Which of the consequences of chronic hyperglycemia contribute to diabetic microangiopathy
PKC activation
AGE production
Where will immature cells be found in HSIL
In the top 2/3 of the epithelium
What are Squamous Intraepithelial Lesions
Cervical precursor lesion associated again with the high-risk HPVs
List common causes of secondary systemic hypertension in children and adolescents (birth to 18 years)
Renal parenchymal disease
Coarctation of the aorta
Breast cancer is due to genetic factors alone - true or false
False
Exact aetiology not well understood but thought to be due to genetic and environmental factors
List potential complications of testicular cancer treatment
Generic chemotherapy complications
Fertility concerns - if only one removed it should be fine, sperm banking can be done and testosterone can be replaced with meds
Surgical complications inc; retrograde ejaculation, impotence and loss of genital and groin sensation
Radiotherapy complications – blistering and peeling around effected site, infertility of healthy testicle effected, increased risk of future cancer, damage to organs and blood vessels near by
How does acute limb ischaemia present
6 Ps – Pain, pallor, pulselessness, paraesthesia, paralysis, poikilothermia (perishingly cold)
List the mechanisms promoting b-cell dysfunction in T2DM
B-cells exhaust their capacity to adapt to insulin resistance and altered BG levels.
Excess FFAs compromise b-cell function and diminish insulin release.
Impact of chronic hyperglycaemia (glucotoxicity)
Abnormal incretin effect: reduced GIP and GLP-1
Amyloid deposition within islets.
What is the most common malignancy in women worldwide
Breast cancer
Also the deadliest
1.7million women are diagnosed annually with 1/3 succumbing to the disease – 20% mortality rare
Most cases of PAD are asymptomatic - true or false
True
Where does the HPV virus mature in the cervix
The mature squamous cells
How are endometroid endometrial carcinomas staged
Currently endometrial cancer is graded based on gland differentiation and presence of squamous foci are largely ignored
Describe the trend with obesity
It is increasing!
Tripled worldwide since 1975
In 2016, more than 1.9 billion adults, 18 years and older, were overweight
List the pancreatic changes that may be seen in T2DM
Subtle decrease in islet cell mass - only seen on special morphometric studies
Amyloid deposits within the islets
Describe the macroscopic features of a testicular choriocarcinoma
Primary tumours are usually small and most often <5cm in diameter
It very common on the cut surface to see both haemorrhage and necrosis
Which symptoms of DKA are caused by ketone bodies themselves
Flushed Vomiting Abdo pain + tenderness Breathless (Kussmaul’s breathing) May have ketone smelling breath but not always
How does hypothyroidism cause renal dysfunction
You gets a reduced kidney-to-body weight ratio which lowers free water clearance and reduces GFR
This causes hyponatremia and leads to higher blood volume
increases BP
How does hypothyroidism increase peripheral vascular resistance
T3 has a vasodilatory effect on vascular muscle cells
This is deficient in hypothyroid so you get peripheral vasoconstriction
Also associated with increased arterial stiffness
Which drugs can cause hypoglycaemia in non-diabetics
insulin oral hypoglycaemics aspirin poisoning ACE-I B-blockers quinine sulphate insulin-like growth factor.
List the main symptoms of hyperthyroidism
Hair thinning/loss Goiters Excessive sweating Shortness of breath High blood pressure
List causes of estrogenic stimulation
Obesity
Menopause
PCOS
Functioning granuloma cell tumours of the ovaries
Excessive ovarian cortical function (stromal hyperplasia)
Prolonged administration of estrogenic substances - oestrogen replacement therapy
What is osteomalacia
Softening of the bones due to inadequate mineralisation, most commonly due to vitamin D deficiency
How does reduced physicals activity cause osteoporosis
Mechanical forces on bone stimulate bone remodelling, therefore immobility or lack of exercise will increase the rate of bone loss
Also contributes to senile osteoporosis as aging is associated with reduced activity
How does renal artery stenosis lead to secondary systemic hypertension
Causes decreased glomerular flow and pressure in afferent arteriole of the glomerulus
This induces renin secretion which causes an increase in blood volume & vascular tone via angiotensin & aldosterone pathways (increase CO & TPR)
List risk factors for testicular cancer
Cryptorchidism Fx of testicular cancer – although most affected males have none Klinefelters syndrome HIV Carcinoma in Situ of the testes Previous testicular cancer – 3-4% risk of another Caucasian Tall ( no link to body weight) Aged 20-34
What effect does insulin have on the striated muscle
Increases glucose uptake, glycogen synthesis and protein synthesis
Which age group is typically affected by serous endometrial carcinoma
Older women
Aged 65-75
Which breast cancers are usually incurable
Those presenting with distant mets
Luckily this is rare
How can sleep apnoea cause secondary systemic hypertension
May be related to sympathetic activation and hormonal changes associated with repeated periods of apnea-induced hypoxia, hypercapnea and stress associated with loss of sleep
If blood results show hypoglycaemia and hyperinsulinemia what is the likely cause
Sulphonylurea or insulin injection
no detectable c-peptide [only released w/ endogenous insulin]
How is SIL graded
Based on the location of these atypical and immature cells
Normal location is in the basal layer
LSIL will have them in the bottom 1/3 of epithelium
HSIL will have them in the top 2/3 as well
What are the main precursor lesions for breast cancer
ductal carcinoma in situ and lobular carcinoma in situ
How is LSIL managed
May just be followed up with repeat tests - chance of regression on its own
May do local ablation of cervix if worried about patient not following up.
Which membrane protein is recruited in the kidney by ADH
Aquaporin 2
Why do hypos need to be reversed quickly
If not you risk neurological damage
Which is more common sporadic of familial breast cancers
Sporadic are much more common
When are GIP and GLP-1 released
Both are released following food ingestion
List the features of proliferative diabetic retinopathy
New vessel formation on fundus - this is the characteristic finding
Can have rubeosis iridis (new vessels on the iridio-corneal angle)
Which specific HPV strains cause the majority of cervical cancer cases
HPV-16 causes 60% of cancer cases and HPV-18 causes another 10%.
In which type of diabetes is DKA more common
Type 1
Less common in T2 due to higher level of portal vein insulin which prevents unrestricted hepatic fatty acid oxidation, keeping ketone bodies in check
Which stains can you do to test for SIL
You can perform in situ hybridisation to look for viral DNA . The majority will be found in upper mature layers and tells you about viral load.
Can also stain for cell proliferation markers and if these are present outside the normal basal location it suggests SIL.
How does Ca2+ nutritional state cause osteoporosis
If Ca2+ intake is insufficient during a period of rapid bone growth (e.g. adolescence), then peak bone mass will be reduced, increasing the risk of osteoporosis later in life
Related to vitamin D deficiency and fluctuations in PTH
Describe the 3 cells that are seen in spermatocytic tumours
Type 1 – they are medium in size and have a round nucleus. They also have spireme type chromatin with occasional nucleoli and the cytoplasm tends to be eosinophilic
Type 2 – these cells tend to be smaller and the chromatin is dense and has a narrow edge of eosinophilc cytoplasm meaning that it looks like a secondary spermatocyte
Type 3 – these are giant cells which are scattered throughout and can either be uninucleate or multinucleate
Describe the life expectancy with breast cancer
It is possible to have a normal life expectancy with breast cancer but can be as low as 10% survival at 5yrs depending on the above features
Huge variation
What is the management for T1DM
Blood glucose and ketone monitoring
Insulin: usually basal [once daily] bolus [with meals] regimen.
Carbohydrate estimation.
Regular check of glycaemic control – HbA1c
Record severe hypoglycaemic episodes or admission with DKA
How is glucose used in the adipose tissue
Primarily used as a substrate for lipid synthesis (stored as triglycerides)
It inhibits triglyceride hydrolysis & lipid release; promoting amino acid uptake & protein synthesis, whilst inhibiting proteolysis.
List other variants of kidney disease seen in diabetics (beside glomerular disease)
Hyalinizing arteriolar sclerosis
Increases susceptibility to pyelonephritis and papillary necrosis and causes various tubular lesions
What happens to the incretin effect in T2 diabetics
It becomes seriously blunted - reduced satiety
Describe treatment for a stage one testicular seminoma
Orchidectomy and single dose of chemo
Potentially radiotherapy also, to reduce recurrence
How can superficial cervical cancer be managed
Treated with cone excision alone.
May also get a large loop excision or trachelectomy (removal of cervix).
Usually for stage 1A or B and aims to remove all cancer.
Sometimes node dissection if in local nodes affected.
Describe stage II serous endometrial carcinoma
Carcinoma involves the corpus and cervix.
Describe the series of events that occur in the baroreceptors when arterial pressure suddenly rises
Vessel walls passively expand
Receptors depolarize - respond to stretch
Increases firing frequency of AP
Vasomotor center inhibits sympathetic drive
and increases vagal tone on SA node of heart
SA node is slowed by Ach
HR slows down
CO decreases
BP decreases
Describe genetic susceptibility in T1DM
30% risk of inheriting T1DM from both parents, and 3x more likely if only father.
40-50% of T1 diabetics are HLA-DR3/DR4 compound heterozygotes.
Those with DR3 or DR4 AND a DQ8 haplotype have highest inherited risk for T1D.
Several non-HLA genes also confer susceptibility – tandem repeats in promoter region of insulin gene and polymorphisms in CTLA4 and PTPN22 causing altered T-cell selection and regulation.
How does phaechromocytoma cause secondary systemic hypertension
Causes high level of circulating catecholamines
This leads to α-adrenoreceptor mediated systemic vasoconstriction + β-adrenoreceptor mediated cardiac stimulation (arrhythmia) Can elevate arterial pressure
How do you diagnose diabetes
Fasting blood glucose ⩾ 7.0mmol/L or
Random blood glucose ⩾ 11.1mmol/L
And symptoms, OR repeat test.
What are the main causes of hypoglycaemia in non-diabetics
EXogenous drugs, alcohol
Pituitary insufficiency
Liver failure
Addison’s disease
Islet cell tumours (insulinoma) and immune hypoglycaemia
Non-pancreatic neoplasms, e.g., fibrosarcoma, hemangiopericytomas.
Use EXPLAIN to remember
What is the main cause of endometrioid endometrial carcinoma
Prolonged and unopposed estrogenic stimulation of the endometrium
Describe the microscopic features of a testicular spermatocytic tumour
They contain 3 cellular populations that are intermixed
They lack inflammatory cells and synctiotrophoblasts
They don’t mix with other GCT types and don’t appear in extra testicular sites
List common causes of secondary systemic hypertension in older adults (65 years and older)
Renal artery stenosis secondary to atherosclerosis
Renal failure
Describe the morphology of non-specialised adenocarcinoma of the breast
Usually 2-3cm in size
Lumps are usually hard, irregular, radio dense and have a desmoplastic stromal reaction
Cutting the tumour creates a grating sound due to small central foci or streaks of chalky white desmoplastic stroma or calcification
Less commonly they can present as well circumscribed and made of sheets of tumour cells - scarce stromal reactions or be almost unperceivable as are made of scattered neoplastic glands or single tumour cells invading fibrofatty tissue
What is dry gangrene
sterile process where tissue becomes mummified
Describe well differentiated endometroid endometrial carcinoma
Composed almost entirely of well formed glands
Serous endometrial carcinoma is associated with a thin physique - true or false
True
What is peripheral artery disease
Specifically refers to the occlusion of the arteries through the formation of atherosclerotic plaques,
Post-pubertal teratomas can progress to what
Teratomas with somatic type malignant transformation
Usually in the form of squamous cell carcinoma, mucin secreting adenoma, sarcoma or another cancer
If not all those HPV get cancer, what other factors influence development
It has been suggested that other factors such as immune status and exposure to other carcinogens may influence whether it progresses.
Describe the obesity grades of the BMI system
Grade 1 overweight (commonly called overweight) - BMI of 25-29.9 kg/m2
Grade 2 overweight (commonly called obesity) - BMI of 30-39.9 kg/m2
Grade 3 overweight (commonly called severe or morbid obesity) - BMI ≥40 kg/m2
Describe the macroscopic features of a testicular embryonal carcinoma
Locally aggressive and often invade the epidydimis, spermatic cord and vascular and lymphatic systems
The cut surface has a variegated appearance due to foci of haemorrhage and necrosis
What is the pathogenesis of T1DM
Genetically susceptible individuals + environmental stimulus leads to b-cell destruction.
Autoantibodies for islet cell antigens attack the cells
What is the gold standard test for peripheral arterial stiffness
Pulse wave velocity (PWV)
If increased its a sign of early vascular ageing
List rarer gene mutations that can cause familial breast cancers
Rarer tumour suppressor genes with germline mutations
Tp53, PTEN, STK11, CDH1, PALPB2, ATM, CHEK2
Describe the appearance of diffuse mesangial sclerosis seen in diabetic nephropathy
lesion consisting of diffuse increase in mesangial matrix
Matrix depositions are PAS-positive, may be nodular as disease progresses
Expansion of mesangium correlates with deteriorating renal function.
How does age affect incidence of osteoporotic fractures
As age increases so does incidence
How do you diagnose endometrial cancer
Diagnosed by histological examination of tissue sample taken via biopsy or curettage (usually with hysteroscopy).
Where is cortisol secreted from
zona fasciculata of adrenal cortex
How does excess thyroid hormone secretion affect the kidneys
Increased kidney mass due to hypertrophy of renal compartments
How does cervical cancer spread
Advanced cancer spreads by direct invasion to contiguous tissue (: paracervical soft tissue, bladder, ureters, rectum and vagina)
It can invade local lymph nodes which then allow for spread to local and distant nodes.
Distant metastases may be seen in liver, lungs, bone marrow and others.
List the macroscopic features of endometroid endometrial carcinoma
Can form a localised polypoid mass or diffusely affect the endometrial lining.
If it invades the broad ligament it can form a palpable mass.
List the microscopic features of osteoporosis
Bone is histologically normal, though there may be noticeably increased osteoclast activity depending on aetiology (seen as pitting on bone surface)
Trabecular bone thins and loses interconnections so vertical trabeculae become more prominent
Describe the volume dependent mechanisms by which sodium retention cause high BP
Excess extracellular volume leads to increased perfusion of peripheral tissues
This stimulates vasoconstriction and increases TPR
Extracellular volume expansion leads to production of ouabain-like steroids that induce vasoconstriction -> increase TPR
What are the most common testicular tumours
Germ cell
Sex chord stromal
When is glucagon released
When glucose is gone
It’s levels fall after a large glucose load
Which cell/tissue types may be found in a teratoma
Islands of cartilage, neural tissue, squamous epithelium lining epidermal like surfaces with or without skin adnexal structures, muscle bundles, bronchial epithelium , structures that look like the thyroid gland, and bits of intestinal wall or brain substance
Describe the epidemiology of testicular choriocarcinomas
1% of GCTS
Highly malignant
Describe endometrial adenosarcomas
Low grade malignancy .
Presents with large polypoid growths that can prolapse through the cervix.
Identified by malignant appearing stroma alongside benign but abnormally shaped glands.
Nearly always confined to the pelvis.
Recurs in 1/4 of cases.
Older women are most effected by which type of breast cancer
Luminal cancer
<2% are HER2+ or Triple neg
Endometrial adenosarcomas are most common in women of what age
In their 40s and 50s
Where is aldosterone secreted from
zona glomerulosa of adrenal gland
How can risk assessment be beneficial for osteoporosis patients
Assessing falls risks in vulnerable or diagnosed populations may reduce the disease burden by reducing the overall number of fractures sustained
What is Addison’s disease
An uncommon disorder resulting from progressive destruction of adrenal cortex - leads to hypofunction
The adrenal glands do not produce enough of the hormone cortisol (& aldosterone) - Chronic adrenocortical insufficiency
Affects about 1 in 100,000 people
Describe the appearance of hepatocyte steatosis caused by obesity
It ranges from that with no evidence of liver injury to non-alcoholic steatohepatitis (NASH) with evidence of inflammation and hepatocyte injury with/without fibrosis.
What is endothelin 1
Most potent vasoconstrictor peptide with marked hypertensive, mitogenic & atherogenic effects
How are Squamous Intraepithelial Lesions classified
As either low or high grade
LSIL = mild dysplasia
HSIL - moderate and severe dysplasia and carcinoma in situ
What are the main causes of hypoglycaemia in diabetic
Insulin or sulphonylurea treatment
Accidental or non-accidental overdose
Increased activity
Missed meal
How are breast cancers staged
Using the Nottingham grading scale
Grades 1-3
How does osteoporosis present
Insidious onset – patients are asymptomatic until fractures occur, and presentation depends on which bones are affected
Fragility fractures
Vertebral fractures -> Back pain, loss of height, deformities (kyphosis)
Which age group is most commonly affected by endometrial carcinoma
Peak is post-menopausal women 55-65
What is Raynaud’s phenomenon
Extremities becoming pale due to decreased blood flow in cold weather
Caused by vasospasm
Do all HPV infections lead to cancer
No
Majority will not cause any symptoms or damage.
How do hyperglycaemia and insulin deficiency lead to glomerulosclerosis
They alter the GBM, largely via non-enzymatic glycation of proteins. Subsequent haemodynamic changes
cause increased GFR, glomerular capillary pressure, and glomerular hypertrophy, which culminate in glomerulosclerosis.
Which endometrial carcinoma is classed as type 2
Serous endometrial carcinoma
The majority of mutations in endometroid endometrial carcinoma act on which pathway
Act to increase signalling by the PI3K/AKT pathway
This enhances the expression of target genes which can be turned on by oestrogen (have oestrogen receptors) in the endometrium.
Removal of which precursor lesion will reduce future risk of invasive cancer
DCIS
Same cannot be said for LCIS
Describe the appearance of nodular glomerulosclerosis (Kimmelstiel-Wilson disease)
Ovoid/spherical lesions
Often laminated
PAS-positive nodules of matrix found in the periphery of a glomerulus.
Sorbitol accumulation in the lens has what effect
Cataract formation
Seen in diabetics
How can cervical cancer be prevented
The HPV vaccine can prevent up to 70% of cases
What are the most important targets of insulin
Striated muscle cells
“beige” adipocytes are another target.
What pressures do the carotid sinus baroreceptors respond to
Respond to pressures ranging from 60-180mmHg
Describe the progression of HSILs
Has a high risk of progressing to cervical carcinoma
Where is ADH released from
Posterior pituitary
It is stored here but made in the hypothalamus
How does Cushing’s suppress vasodilatory systems
Glucocorticoids inhibit NOS synthesis which produces the vasodilator NO
As a result TPR increases and so does BP
Glucocorticoids also inhibit production of prostacyclin (another potent vasodilator in vascular endothelium)
Decreased PGE2 & kallikrein
Mutations in which gene is commonly seen in serous endometrial carcinoma
Highly associated with mutations in the TP53 tumour suppressor gene (present in over 90% of these tumours).
These mutations are also found in the precursor lesion which suggests they are an early occurrence in the natural history of these tumours.
Also have high chromosomal instabaility – a feature of TP53 cancers.
List the features of nephrotic syndrome
Proteinuria >3g/day Hypoalbinaemia (<30) Oedema Hypercholesterolaemia Usually normal renal function
What is meant by a mixed testicular tumour
Tumour is composed of >1 type of GCT
Accounts for 60% of all GCTs
List symptoms of Cushing’s
Psychosis Impaired memory Sleep disturbance Depression and anxiety Hypertension Dyslipidaemia Obesity Facial and abdominal fat accumulation Diabetes - impaired glucose tolerance Muscle and skin atrophy Osteoporosis
Which conditions of adrenocortical hyperfunction can cause secondary systemic hypertension
Cushing syndrome
Primary aldosteronism
Congenital adrenal hyperplasia
Licorice ingestion
Describe the epidemiology of endometrial carcinoma
Accounts for 7% of all invasive cancer in women.
Used to be much less common than cervical but the screening program and increased incidence of endometrial cancer in young women has switched this.
There were 380,000 new cases in 2018 worldwide
List potential complications of radiotherapy
skin breakdown, angiosarcoma of the breast skin, breast and arm lymphoedema, radiation fibrosis of the breast, chronic radiation pneumonitis, chronic pericarditis, chronic discolouration of the effected area, osteoporosis
How does behaviour contribute to obesity
Inactivity and not getting enough exercise
Not burning off enough calories
People in the UK are much less active now
Which haplotype has the greatest risk of T1DM
DR3 or DR4 AND a DQ8 haplotype
18- fold increase
Describe the microscopic features of a testicular choriocarcinoma
These tumours are mainly composed of syncytiotrophoblasts and cytotrophoblasts
What is the purpose of neoadjuvant therapy in breast cancer
Used to downstage cancer, reduce nodal involvement and improve surgical outcomes
Can be chemotherapy, endocrine therapy or biologic therapy but not radiotherapy
Young women are most effected by which type of breast cancer
Mainly have HER2+ or Triple neg
Rarely affected by luminal cancer
How can you treat osteoporosis
Bisphosphonates – Inhibit osteoclastic bone resorption
Denosumab – Anti-RANKL monoclonal antibody
Hormone Therapy - Selective Oestrogen Receptor Modulator (SERM) or HRT
List common causes of secondary systemic hypertension in middle aged adults (40-64)
Hyper aldosteronism
Obstructive sleep apnoea
Cushing’s syndrome
Phaeochromocytoma
What are the main types of testicular sex chord stromal tumours
Leydig and Sertoli cell tumours
Leydig cell tumours are the most common of the 2 in children and adults
What effect does insulin have on the liver
Decreases gluconeogenesis
Increased glycogen synthesis and lipogenesis
How do you treat hypoglycaemia
If conscious, orientated & able to swallow: 15-20g quick-acting CHO snack (200ml orange juice) and recheck BG after 20-25mins (repeat up to 3 times).
If conscious but uncooperative, squirt glucose gel between teeth & gums.
If unconscious/unresponsive to above measures: glucose IV (10% at 200ml/hr if conscious; 200ml/15mins if unconscious) or give glucagon 1mg IV/IM (wont work in malnourished patients).
How do you diagnose a hypo
Bloods: glucose, insulin, c-peptide, plasma ketones (symptomatic).
If endogenous hyperinsulinism suspected – insulin, c-peptide, proinsulin, beta-hydroxybutyrate.
How does Addison’s disease affect BP
Lack of cortisol and aldosterone secretion reduces the BP
How can the incretin effect be harnessed to treat T2 DM
Efforts to restore incretin function can lead better control of BG and promotes weight loss (by restoring satiety)
This has led to development of DPP4-inhibitors and GLP-1 agonists for T2D treatment.
PTEN mutations (tumour suppressor) have been identified in both hyperplastic lesions and the carcinoma - true or false
True
This suggests suggesting some of the mutations occur before it becomes cancerous
Describe the glucose levels inside and outside of insulin dependent cells in diabetes
low glucose inside cell, high glucose outside cell
Seen in skeletal muscle, adipose tissues, liver
What is the main underlying cause for all diabetes complications
Persistent hyperglycaemia
Leads to glucotoxicity
List the microscopic features of endometroid endometrial carcinoma
Endometrioid microscopic pattern with glandular, cribriform, and papillary features
These cancers have 3 histological patterns of glandular growth: well differentiated, moderately differentiated and poorly differentiated
Some tumours have foci of squamous differentrion (around 20%)
Describe stage 1 cervical cancer
Carcinoma is confined to the cervix.
Further divided into:
1a – preclinical carcinoma diagnosed only by microscopy
1a1 – stromal invasion no deeper than 3mm and no wider than 7mm (also called superficially invasive)
1a2 – depth of stromal invasion between 3mm and 5mm, no wider than 7mm (horizontal invasion
1b – Histologically invasive carcinoma, still confined to cervix but greater than 1a2
Which nerve signals to the veins can lead to a drop in BP
Decrease sympathetic tone on veins
Compliance increases so venous pressure decreases
This causes VR to decrease and CO decreases as a result
Overall BP decreases
What happens when AQP2 fuses with the apical membrane in the kidney tubules
AQP-2 gene expression increases
Collecting duct epithelium becomes permeable to water
More H2O resorbed through osmosis
This leads to more concentrated urine
BV returns to normal (increased arterial pressure)
How is intermittent claudication managed
Encourage patients to continue walking - may find supervised exercise programmes beneficial
In patients with lifestyle-limiting disease, additional pharmacological treatment should be offered
Cilostazol – Vasodilator with antiplatelet action
contraindicated in CCF and recent ACS
What is metabolic syndrome
It is a cluster of conditions that occur together, increasing your risk of heart disease, stroke and type 2 diabetes.
The conditions include increased blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol or triglyceride levels.
Causes abnormalities of glucose and lipid metabolism coupled with hypertension and evidence of a systemic pro-inflammatory state.
Crystalloids of Reinke are characteristic of which tumour type
Leydig cell tumours
What is the most common subtype of germ cell tumour in the testes
Seminomas
Long standing diabetes is associated with which eye diseases
Raised intra-ocular pressure = glaucoma
Damage to the optic nerve
What initial tests would you do in a middle aged adult with secondary systemic hypertension
Renin and aldosterone levels
TSH
Polysomnography if OSA suspected cause
24hr urinary cortisol and fractionated metanephrines if above tests inconclusive
How do serous endometrial carcinomas develop
The tumours begin as surface epithelial neoplasms which then extend into adjacent glands and later the endometrial stroma.
They also have a propensity to break off and travel through the fallopian tubes and implant on peritoneal structures.
What initial tests would you do in an older adult with secondary systemic hypertension
Renal artery doppler MRA with contrast CT angiography TSH Urinalysis
How does angiotensin 2 act on the blood brain barrier
Acts on AT receptors there - particularly high density in brain areas responsible for CVS regulation
Acts on 3 circumventricular organs of brain which send signals to other areas of brain
This increases SNS activity and modulates baroreflex sensitivity -> increase BP
What factor affects the prevalence of diabetic neuropathy
Duration of disease
Up to 50% of all diabetics have it but in those who have had diabetes for >15years prevalence is up to 80%
What is DKA
Diabetic ketoacidosis
A disordered metabolic state usually occurring in the context of an absolute or relative insulin deficiency accompanied by an increase in the counter-regulatory hormones (glucagon, adrenaline, cortisol, GH).
Describe the epidemiology of PAD
Around 20% of >60s in the UK are estimated to have some degree of PAD
But this is difficult to quantify as roughly half these patients will be asymptomatic
Describe the epidemiology of testicular yolk sac tumours
Prepubertal ones tend to be pure with good prognosis
Most common tumour in <3yrs
But post-pubertal are mixed
List the macroscopic features of serous endometrial carcinomas
Large and bulky tumours (may look larger as typically occur in atrophic uteri).
May have deeply invaded the myometrium.
Endometrial adenosarcomas need to be differentiated from which other condition
Diagnosis mainly involves differentiating from benign polyps.
They have the same gross appearance but the cancer has malignant stroma and benign but abnormally shaped glands.
List the pathological features of Cervical neuroendocrine tumours
Appears similar to small cell lung cancer but will also test positive for high-risk HPV.
At which point does maximal carotid sinus sensitivity occur
Maximal carotid sinus sensitivity occurs near the normal mean arterial pressure
Therefore, very small changes in arterial pressure around this set point alters receptor firing
How can stress lead to secondary systemic hypertension
Emotional stress activates the sympathetic nervous system
You get an increase in norepinephrine release from sympathetic nerves in heart and blood vessels which increases CO and TPR
Adrenal medulla secretes more catecholamines -this activate sympathetic nervous system and increases circulating angiotensin II, aldosterone, vasopressin
All increase TPR
List common symptoms of testicular cancer
Most cases present with a testicular lump or enlarged testicle - usually hard, within the testicle, non transluminal and able to be gotten above
Usually painless but may have episodic pain due to haemorrhage
Dragging sensation in the scrotum
A hydrocele may also be present and potentially filled with blood stained fluid – it can also invade into the scrotum
Describe the effect of TP53 mutations
Leads to accumulation of altered p53 proteins
What initial tests would you do in a child/adolescent with secondary systemic hypertension
Urinalysis
Urine culture
Renal ultrasound
Echo if above tests not conclusive
What treatments may become available for endometrial cancer in the future
A lot of research is going into biological agents that target specific pathways associated with these cancers. At the moment inhibitors of the PI3K/AKT pathway are in clinical trials
How does ADH act on the renal collecting ducts to increase BP
Acts on them via V3 receptors
This increase water permeability (cAMP-dependent mechanism) and therefore decrease urine formation
This causes an increase blood volume & CO so arterial pressure increases
Gluconeogenesis is a constantly occurring process - true or false
True
It provides energy to tissues such as skeletal muscle, brain and adipose tissue, cardiac muscle – tissues requiring glucose but can’t make it themselves.
Which endometrial carcinoma is classed as type 1
Endometroid endometrial carcinoma
Describe the microscopic features of a Leydig cell tumour
Histologically cells look like normal Leydig cells - round or polygonal cell outlines, usually large, round and central nucleus and cytoplasm is granular and eosinophilic
Lipid droplets, vacoules or lipofuscin pigment are found in the cells cytoplasm along with rod shaped crystalloids of Reinke which are characteristic of this tumour and seen in about ¼ of them
What are the symptoms of endometrial cancer
May be asymptomatic.
Main symptom is abnormal vaginal bleeding: either irregular or post-menopausal.
Less common symptoms are pain in the lower abdomen and pain during sex
Why is the transformation zone susceptible to cancer development
Immature squamous cells developing here which are highly susceptible to HPV infection (major cause of cervical cancer)
How are endometrioid endometrial carcinomas managed
Endometroid carcinomas are typically treated with surgery (often a hysterectomy)
They may also receive adjuvant radiotherapy to prevent recurrence and chemotherapy if it has spread outside of the uterus.
Breast cancer affects which age groups
Rare in women <25yrs and more common after 30
Which part of the cervix can be seen on speculum examination
The ectocervix
Which glomerular lesions are seen in diabetic nephropathy
Capillary basement membrane thickening
Diffuse mesangial sclerosis
Nodular glomerulosclerosis (Kimmelstiel-Wilson disease)
What innervates the carotid sinus baroreceptors
The sinus nerve of hering
Branch of the glossopharyngeal nerve which synapses in the NTS in the medulla
List the pathological features of Cervical adenosquamous cancer
Composed of a mix of malignant squamous and glandular epithelium.
Describe stage III serous endometrial carcinoma
Carcinoma extends outside of the uterus but not outside the true pelvis.
What is osteoporosis
A skeletal disease characterised by low bone mineral density and abnormal bone architecture, resulting in increasingly fragile bone and elevated fracture risk
Where do most cervical cancers form
The transformation zone
What are the most common sites of fracture in osteoporosis
vertebrae, proximal femur and distal radius
Describe the volume independent mechanisms by which sodium retention cause high BP
increased vascular stiffness & increased central sympathetic outflow
What are the risk factors for obesity
Increased production and intake of energy-dense foods that are high in fat and sugars
Decrease in physical activity - increasingly sedentary nature of many forms of work, modes of transportation, and increasing urbanization
Dietary habits
Social deprivation
Income
Ethnicity
What is the definition of obesity
“an accumulation of adipose tissue of sufficient magnitude to impair health”
Overweight and obesity are terms that refer to an excess of body fat and usually relate to increased weight-for-height
Secondary systemic hypertension is the most common type of hypertension seen - true or false
False
Makes up only a small fraction (5-10%) of hypertensive cases
ADH is first secreted into which vessel
inferior hypophyseal artery
Why does serous endometrial carcinomas have a poor prognosis
They also have a propensity to break off and travel through the fallopian tubes and implant on peritoneal structures
Therefore often outside of the uterus by the time of diagnosis
Endocrine therapy can be extended for how long
Both forms of adjuvant endocrine therapy can be extended and so are used for more than 5yrs but postmenopausal women get acromatase inhibitors and premenopausal get tamoxifen
Even if low risk of recurrence post menopausal women can still get extended endocrine therapy
How does endometroid endometrial carcinoma progress and spread
Start with precursor lesions then develop into the carcinoma.
Spread generally occurs by direct invasion of myometrium and other surrounding structures/organs.
Eventually it will spread to the regional lymph nodes.
Late stages involves metastases to the lungs, liver, bones and other organs.
List the biochemical signs of DKA
Ketonaemia >3mmol/L, or significant ketonuria (>2+ on urine stick)
BG >11.0mmol/L (or known diabetes)
Bicarbonate <15mmol/L or venous pH <7.3.
Autoantibodies against islet antigens are found in most T1 diabetics - true or false
True
However, it is unclear if the autoantibodies are causing the injury or if they are merely a consequence of islet injury
If causing injury there may be a role for antibodies in the treatment of the disease
What other diseases can HPV cause other than cervical cancer
Also causes other cancers such as vulvar, penile, anal, vaginal and oropharyngeal
Low risk strains can cause genital warts
Which lifestyle factors can increase the risk of cervical cancer
Cigarette smoking
Linked to 20% of cases
Where does coarctation of the aorta most commonly occur
just distal to left subclavian artery in the arch of aorta
Where is leptin produced
Fat cells
Which biochemical factors must be monitored in HHS
Monitor and chart BG, osmolality and Na every 1-2hrs
Monitor fluid input and output
How are serous endometrial carcinomas managed
Serous carcinomas are aggressive in nature so usually treated with chemotherapy even if there is no evidence of spread yet alongside the other treatments.
How does Cushing’s affect β-Adrenergic Receptors
Increases their sensitivity to catecholamines
The SNS is upregulated and you get increased vascular tone
This increased BP
Obese people are at higher risk of a severe response to COVID - true or false
True - a clear link has already been established
It increases the risk of dying from the disease by nearly 50% and may make vaccines less effective
What determines the prognosis of serous endometrial carcinoma
Highly dependent on the stage
How does angiotensin II raise BP
Acts on the AT1 receptor to induce vascular contraction
Stimulates aldosterone secretion
Increases sodium resorption
Acts on the blood brain barrier
If blood results show low or undetectable insulin and no excess ketones what is the likely cause of the hypo
Non-pancreatic neoplasm
Anti-insulin receptor antibodies
What is acute limb ischaemia
Sudden occlusion of vessels which threatens limb viability
Usually due to thromboembolism
What are the subtypes of endometrial carcinoma
Endometrioid Endometrial Carcinoma
Accounts for 80-85% of cases
Also called type 1 carcinoma
Serous Endometrial Carcinoma
Account for 15% of cases
Also called type 2 carcinoma
What types of HPV are covered by the vaccine
Protects against both high and low risk HPV - reduces cancer and warts.
There are different types of HPV vaccine but the most comprehensive is Gardasil 9 (it covers HPV-16,18,31,33,45,52 and 58 and low risk HPV-6 and 11)
List consequences of bisphosphonate treatment
Osteonecrosis of the jaw and atypical fractures are known risks
Which symptoms of DKA are caused by osmotic disruption
Thirst, polyuria
Dehydration
Fatigue
How is advanced cervical cancer managed
Advanced lesions also treated with radiation and chemotherapy.
Pelvic exenteration may be done if other options have failed. This is removal of pelvic organs and some surrounding tissues.
Advanced cancer is often considered incurable/palliative, so patients are treated with chemo and a drug called Avastin (bevacizumab) to try and control the cancer.
Describe the progression of LSILs
Low-grade doesn’t directly progress to invasive cancer, in fact many cases will spontaneously regress.
Only a small percentage move onto high-grade.
What investigations are performed if a smear test comes back abnormal
You get a colposcopy to examine the cervix and identify the lesion.
Acetic acid is applied as this causes abnormal epithelium to show up as white spots.
Abnormal areas can then be biopsied.
How is critical limb ischaemia managed
If patient is suitable for revascularisation, this can be achieved via endovascular or surgical methods
If not patients should be closely monitored in case amputation required and risk factors managed
How does sleep deprivation and circadian disruption contribute to T2DM
CD impairs glucose haemostasis by affecting both insulin secretion and action
Association found between circadian-controlled genes and T2D
Disruption of “clock” genes not only affects insulin secretion & action but also activity level and feeding behaviors
This leads to increased risk of hyperglycaemia and diabetes
Which neurological conditions can cause secondary systemic hypertension
Psychogenic - brought on by stress
Increased cranial pressure
Sleep apnoea
Acute stress, including surgery
What are the complications of endometrial cancer treatment
Typical side effects of hysterectomy, chemo and radiotherapy
Progesterone therapy can cause mild nausea, mild muscle cramps and weight gain
How is advanced breast cancer managed
A combination of chemotherapy, endocrine therapy and biological therapy rather than surgery due to the nature of the disease
List some of the clinical consequences of obesity
Cardiovascular - Coronary artery disease, hypertension, LVH, cor pulmonale, obesity-associated cardiomyopathy, accelerated atherosclerosis, and pulmonary hypertension of obesity
Respiratory - OSA,greater predisposition to respiratory infections, increased incidence of bronchial asthma, and Pickwickian syndrome (obesity hypoventilation syndrome)
Gastrointestinal - Gall bladder disease (cholecystitis, cholelithiasis e.g. gallstones), non-alcoholic steatohepatitis (NASH), fatty liver infiltration, and reflux oesophagitis
Cancer
Depression and stress
Arthritis
What is the common mechanism of death from testicular cancer
Complications of metastasis
Describe the macroscopic features of a testicular seminoma
Bulky mass up to 10X size of normal testes
Homogenous gray/white lobulated cut surface without haemorrhage or necrosis
Can extend to epididymis, spermatic cord and scrotal sac
What does the AGE-RAGE complex cause in diabetics
Release of cytokines + growth factors.
ROS generated in endothelial cells.
Increased procoagulant activity on ECs + macrophages.
Increased proliferation of vascular SMCs + ECM synthesis
In the UK how many people will develop cervical cancer in their lifetime
Less than 1% of those with a cervix
Protein linking by AGEs has what effects
Proteins cross-linked by AGEs resist digestion so they accumulate in the cells
Can also reduce elasticity of vessels - type 1 collagen
Which genes/proteins have been linked to post-menopausal osteoporosis
RANKL – Expressed by osteoblasts
RANK – Facilitates osteoclast formation, function and differentiation
OPG – Secreted by osteoblasts and inhibits the RANKL-induced activation of RANK
What treatment is offered to carriers of the BRACA genes
Prophylactic mastectomy and salpingoophrectomy
Reduces mortality
