Seminar 7 - Endocrine Disease and Its Complications

Question 1

Which tests can be done to identify the specific type of diabetes

Answer 1

Often T1 is diagnosed on Hx and PC alone (e.g., DKA)

If in doubt, GAD/IA2 antibodies [and c-peptide] may help

Question 2

What is Cushing’s syndrome

Answer 2

A disease resulting from chronic excess of glucocorticoids

Question 3

Why is endometrial cancer often diagnosed early

Answer 3

Post-menopausal bleeding is a common symptom which many women know to have checked so it often leads to early detection and good prognosis.

Question 4

Which differentials must you consider when diagnosing osteoporosis

Answer 4

Metastatic bone malignancy
Osteomalacia – Difficult to differentiate clinically
Multiple myeloma – Symptoms include bone pain as well as those of anaemia and renal failure

Question 5

Cervical cancer can affect your sex life - true or false

Answer 5

True
Can be due to treatment side effects or psychological/emotional
Also cannot have vaginal sex for a time after surgery

Question 6

What is the precursor lesion for serous endometrial carcinoma

Answer 6

Endometrial intraepithelial carcinoma.

Question 7

What determines the outcome of breast cancer

Answer 7

The stage at presentation
Biological features - e.g. whether it is ER, HER2 of triple neg
Histological type

Question 8

Which type of adjuvant therapies are available for breast cancer

Answer 8

Chemotherapy
Biological therapies - trastuzumab/Herceptin
Endocrine therapies - tamoxifen

Question 9

List the macroscopic features of osteoporosis

Answer 9

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

Question 10

What is hyperosmolar hyperglycaemia syndrome

Answer 10

Hypovolaemia and hyperglycaemia without significant acidosis or ketonemia (non-ketotic state)
Also hyperosmolar.

Question 11

List symptoms that may be seen in advanced stage endometrial cancer

Answer 11

Patients may experience: pain in the back, legs or pelvis, loss of appetite, tiredness and nausea

Question 12

In which age group is secondary systemic hypertension more common

Answer 12

More common in younger persons, with a prevalence close to 30% in those 18 to 40 years of age with hypertension

Question 13

List the pathological features of Cervical adenocarcinoma

Answer 13

Characterised by proliferation of glandular epithelium composed of malignant endocervical cells.
These cells have large hyperchromatic nuclei (darker appearance) and relatively mucin depleted cytoplasm.

Question 14

Describe the epidemiology of cervical cancer

Answer 14

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

Question 15

What is insulitis

Answer 15

The leukocytic infiltrates in islets seen in T1DM

Contributes to destruction of the islets

Question 16

Diffuse thickening of the basement membrane underlies the development of which diabetic complications

Answer 16

Diabetic nephropathy, retinopathy and some forms of neuropathy

Question 17

Development of end-stage renal disease is more common in which type of diabetes

Answer 17

Type 1

ESRD occurs in >75% of T1 diabetics (vs. 40% T2) within 20 years of developing nephropathy.

Question 18

List cardiovascular causes of secondary systemic hypertension

Answer 18

Coarctation of the aorta 
Polyarteritis nodosa
Increased intravascular volume
Increased cardiac output
Rigidity of the aorta

Question 19

Which symptoms of diabetes are caused by the lack of anabolic action from insulin

Answer 19

Results in catabolic effects so you get:
Increased appetite
Weight loss
Muscle weakness

Question 20

How does angiotensin II stimulate aldosterone secretion

Answer 20

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

Question 21

What is happening to the global prevalence of diabetes

Answer 21

It is rising

rose from 108 million (1980) to 422 million (8.5%; 2014

Question 22

List the microscopic features of serous endometrial carcinomas

Answer 22

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.

Question 23

In which ethnic groups is breast cancer most common

Answer 23

Risk is highest for European women

4-7x greater risk than rest of population

Question 24

What are the 3 main groups of breast cancer and how are they grouped

Answer 24

Grouped by protein expression

HER2+ – positive for HER2 and +/- for ER
Triple negative – negative for ER, HER2 and PR
Luminal – ER + and HER2 negative

Question 25

List the pathological features of Cervical squamous cell carcinoma

Answer 25

Composed of nests or tongues of malignant epithelium. Can be keratinising or non keratinising. These nests can invade the underlying cervical stroma.

Question 26

List complications of testicular cancer metastasis

Answer 26

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

Question 27

Premature birth or miscarriage due to cervical excision surgery is common -true or false

Answer 27

False | It is rare - only occurs in 2% of women who have had the procedure

Question 28

How do Selective Oestrogen Receptor Modulator (SERM) work in osteoporosis

Answer 28

Only appears effective in reducing vertebral fractures

Question 29

How can you differentiate well differentiated endometroid endometrial carcinoma from endometrial hyperplasia

Answer 29

Can be differentiated from hyperplasia by presence of complex growth patterns (e.g. papillary) or desmoplastic stroma

Question 30

In which % of secondary hypertension patients have Cushing's

Answer 30

~80% of adult patients | ~47% in children

Question 31

What additional risks need to be addressed in DKA

Answer 31

Is a NG tube required? Monitor K+ Prescribe LMWH Source sepsis if present: CXR, cultures

Question 32

Does diabetic neuropathy mainly effect sensory or motor neurons

Answer 32

Sensory

Question 33

Which medications can increase the risk of cervical cancer

Answer 33

Oral contraceptives | Increase risk in those already infected with HPV

Question 34

How does the brain regulate food intake

Answer 34

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

Question 35

Which hormones are commonly released by Leydig cell tumours

Answer 35

Cells commonly release androgens, estrogen and corticosteroids

Question 36

Which of the consequences of chronic hyperglycemia contribute to diabetic microangiopathy

Answer 36

PKC activation | AGE production

Question 37

Where will immature cells be found in HSIL

Answer 37

In the top 2/3 of the epithelium

Question 38

What are Squamous Intraepithelial Lesions

Answer 38

Cervical precursor lesion associated again with the high-risk HPVs

Question 39

List common causes of secondary systemic hypertension in children and adolescents (birth to 18 years)

Answer 39

Renal parenchymal disease | Coarctation of the aorta

Question 40

Breast cancer is due to genetic factors alone - true or false

Answer 40

False | Exact aetiology not well understood but thought to be due to genetic and environmental factors

Question 41

List potential complications of testicular cancer treatment

Answer 41

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

Question 42

How does acute limb ischaemia present

Answer 42

6 Ps – Pain, pallor, pulselessness, paraesthesia, paralysis, poikilothermia (perishingly cold)

Question 43

List the mechanisms promoting b-cell dysfunction in T2DM

Answer 43

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.

Question 44

What is the most common malignancy in women worldwide

Answer 44

Breast cancer Also the deadliest 1.7million women are diagnosed annually with 1/3 succumbing to the disease – 20% mortality rare

Question 45

Most cases of PAD are asymptomatic - true or false

Answer 45

True

Question 46

Where does the HPV virus mature in the cervix

Answer 46

The mature squamous cells

Question 47

How are endometroid endometrial carcinomas staged

Answer 47

Currently endometrial cancer is graded based on gland differentiation and presence of squamous foci are largely ignored

Question 48

Describe the trend with obesity

Answer 48

It is increasing! Tripled worldwide since 1975 In 2016, more than 1.9 billion adults, 18 years and older, were overweight

Question 49

List the pancreatic changes that may be seen in T2DM

Answer 49

Subtle decrease in islet cell mass - only seen on special morphometric studies Amyloid deposits within the islets

Question 50

Describe the macroscopic features of a testicular choriocarcinoma

Answer 50

Primary tumours are usually small and most often <5cm in diameter It very common on the cut surface to see both haemorrhage and necrosis

Question 51

Which symptoms of DKA are caused by ketone bodies themselves

Answer 51

``` Flushed Vomiting Abdo pain + tenderness Breathless (Kussmaul’s breathing) May have ketone smelling breath but not always ```

Question 52

How does hypothyroidism cause renal dysfunction

Answer 52

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

Question 53

How does hypothyroidism increase peripheral vascular resistance

Answer 53

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

Question 54

Which drugs can cause hypoglycaemia in non-diabetics

Answer 54

``` insulin oral hypoglycaemics aspirin poisoning ACE-I B-blockers quinine sulphate insulin-like growth factor. ```

Question 55

List the main symptoms of hyperthyroidism

Answer 55

``` Hair thinning/loss Goiters Excessive sweating Shortness of breath High blood pressure ```

Question 56

List causes of estrogenic stimulation

Answer 56

Obesity Menopause PCOS Functioning granuloma cell tumours of the ovaries Excessive ovarian cortical function (stromal hyperplasia) Prolonged administration of estrogenic substances - oestrogen replacement therapy

Question 57

What is osteomalacia

Answer 57

Softening of the bones due to inadequate mineralisation, most commonly due to vitamin D deficiency

Question 58

How does reduced physicals activity cause osteoporosis

Answer 58

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

Question 59

How does renal artery stenosis lead to secondary systemic hypertension

Answer 59

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)

Question 60

List risk factors for testicular cancer

Answer 60

``` 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 ```

Question 61

What effect does insulin have on the striated muscle

Answer 61

Increases glucose uptake, glycogen synthesis and protein synthesis

Question 62

Which age group is typically affected by serous endometrial carcinoma

Answer 62

Older women | Aged 65-75

Question 63

Which breast cancers are usually incurable

Answer 63

Those presenting with distant mets | Luckily this is rare

Question 64

How can sleep apnoea cause secondary systemic hypertension

Answer 64

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

Question 65

If blood results show hypoglycaemia and hyperinsulinemia what is the likely cause

Answer 65

Sulphonylurea or insulin injection | no detectable c-peptide [only released w/ endogenous insulin]

Question 66

How is SIL graded

Answer 66

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

Question 67

What are the main precursor lesions for breast cancer

Answer 67

ductal carcinoma in situ and lobular carcinoma in situ

Question 68

How is LSIL managed

Answer 68

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.

Question 69

Which membrane protein is recruited in the kidney by ADH

Answer 69

Aquaporin 2

Question 70

Why do hypos need to be reversed quickly

Answer 70

If not you risk neurological damage

Question 71

Which is more common sporadic of familial breast cancers

Answer 71

Sporadic are much more common

Question 72

When are GIP and GLP-1 released

Answer 72

Both are released following food ingestion

Question 73

List the features of proliferative diabetic retinopathy

Answer 73

New vessel formation on fundus - this is the characteristic finding Can have rubeosis iridis (new vessels on the iridio-corneal angle)

Question 74

Which specific HPV strains cause the majority of cervical cancer cases

Answer 74

HPV-16 causes 60% of cancer cases and HPV-18 causes another 10%.

Question 75

In which type of diabetes is DKA more common

Answer 75

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

Question 76

Which stains can you do to test for SIL

Answer 76

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.

Question 77

How does Ca2+ nutritional state cause osteoporosis

Answer 77

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

Question 78

Describe the 3 cells that are seen in spermatocytic tumours

Answer 78

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

Question 79

Describe the life expectancy with breast cancer

Answer 79

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

Question 80

What is the management for T1DM

Answer 80

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

Question 81

How is glucose used in the adipose tissue

Answer 81

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.

Question 82

List other variants of kidney disease seen in diabetics (beside glomerular disease)

Answer 82

Hyalinizing arteriolar sclerosis | Increases susceptibility to pyelonephritis and papillary necrosis and causes various tubular lesions

Question 83

What happens to the incretin effect in T2 diabetics

Answer 83

It becomes seriously blunted - reduced satiety

Question 84

Describe treatment for a stage one testicular seminoma

Answer 84

Orchidectomy and single dose of chemo | Potentially radiotherapy also, to reduce recurrence

Question 85

How can superficial cervical cancer be managed

Answer 85

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.

Question 86

Describe stage II serous endometrial carcinoma

Answer 86

Carcinoma involves the corpus and cervix.

Question 87

Describe the series of events that occur in the baroreceptors when arterial pressure suddenly rises

Answer 87

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

Question 88

Describe genetic susceptibility in T1DM

Answer 88

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.

Question 89

How does phaechromocytoma cause secondary systemic hypertension

Answer 89

Causes high level of circulating catecholamines This leads to α-adrenoreceptor mediated systemic vasoconstriction + β-adrenoreceptor mediated cardiac stimulation (arrhythmia) Can elevate arterial pressure

Question 90

How do you diagnose diabetes

Answer 90

Fasting blood glucose ⩾ 7.0mmol/L or Random blood glucose ⩾ 11.1mmol/L And symptoms, OR repeat test.

Question 91

What are the main causes of hypoglycaemia in non-diabetics

Answer 91

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

Question 92

What is the main cause of endometrioid endometrial carcinoma

Answer 92

Prolonged and unopposed estrogenic stimulation of the endometrium

Question 93

Describe the microscopic features of a testicular spermatocytic tumour

Answer 93

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

Question 94

List common causes of secondary systemic hypertension in older adults (65 years and older)

Answer 94

Renal artery stenosis secondary to atherosclerosis | Renal failure

Question 95

Describe the morphology of non-specialised adenocarcinoma of the breast

Answer 95

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

Question 96

What is dry gangrene

Answer 96

sterile process where tissue becomes mummified

Question 97

Describe well differentiated endometroid endometrial carcinoma

Answer 97

Composed almost entirely of well formed glands

Question 98

Serous endometrial carcinoma is associated with a thin physique - true or false

Answer 98

True

Question 99

What is peripheral artery disease

Answer 99

Specifically refers to the occlusion of the arteries through the formation of atherosclerotic plaques,

Question 100

Post-pubertal teratomas can progress to what

Answer 100

Teratomas with somatic type malignant transformation | Usually in the form of squamous cell carcinoma, mucin secreting adenoma, sarcoma or another cancer

Question 101

If not all those HPV get cancer, what other factors influence development

Answer 101

It has been suggested that other factors such as immune status and exposure to other carcinogens may influence whether it progresses.

Question 102

Describe the obesity grades of the BMI system

Answer 102

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

Question 103

Describe the macroscopic features of a testicular embryonal carcinoma

Answer 103

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

Question 104

What is the pathogenesis of T1DM

Answer 104

Genetically susceptible individuals + environmental stimulus leads to b-cell destruction. Autoantibodies for islet cell antigens attack the cells

Question 105

What is the gold standard test for peripheral arterial stiffness

Answer 105

Pulse wave velocity (PWV) | If increased its a sign of early vascular ageing

Question 106

List rarer gene mutations that can cause familial breast cancers

Answer 106

Rarer tumour suppressor genes with germline mutations | Tp53, PTEN, STK11, CDH1, PALPB2, ATM, CHEK2

Question 107

Describe the appearance of diffuse mesangial sclerosis seen in diabetic nephropathy

Answer 107

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.

Question 108

How does age affect incidence of osteoporotic fractures

Answer 108

As age increases so does incidence

Question 109

How do you diagnose endometrial cancer

Answer 109

Diagnosed by histological examination of tissue sample taken via biopsy or curettage (usually with hysteroscopy).

Question 110

Where is cortisol secreted from

Answer 110

zona fasciculata of adrenal cortex

Question 111

How does excess thyroid hormone secretion affect the kidneys

Answer 111

Increased kidney mass due to hypertrophy of renal compartments

Question 112

How does cervical cancer spread

Answer 112

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.

Question 113

List the macroscopic features of endometroid endometrial carcinoma

Answer 113

Can form a localised polypoid mass or diffusely affect the endometrial lining. If it invades the broad ligament it can form a palpable mass.

Question 114

List the microscopic features of osteoporosis

Answer 114

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

Question 115

Describe the volume dependent mechanisms by which sodium retention cause high BP

Answer 115

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

Question 116

What are the most common testicular tumours

Answer 116

Germ cell | Sex chord stromal

Question 117

When is glucagon released

Answer 117

When glucose is gone | It's levels fall after a large glucose load

Question 118

Which cell/tissue types may be found in a teratoma

Answer 118

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

Question 119

Describe the epidemiology of testicular choriocarcinomas

Answer 119

1% of GCTS | Highly malignant

Question 120

Describe endometrial adenosarcomas

Answer 120

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.

Question 121

Older women are most effected by which type of breast cancer

Answer 121

Luminal cancer <2% are HER2+ or Triple neg

Question 122

Endometrial adenosarcomas are most common in women of what age

Answer 122

In their 40s and 50s

Question 123

Where is aldosterone secreted from

Answer 123

zona glomerulosa of adrenal gland

Question 124

How can risk assessment be beneficial for osteoporosis patients

Answer 124

Assessing falls risks in vulnerable or diagnosed populations may reduce the disease burden by reducing the overall number of fractures sustained

Question 125

What is Addison's disease

Answer 125

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

Question 126

Describe the appearance of hepatocyte steatosis caused by obesity

Answer 126

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.

Question 127

What is endothelin 1

Answer 127

Most potent vasoconstrictor peptide with marked hypertensive, mitogenic & atherogenic effects

Question 128

How are Squamous Intraepithelial Lesions classified

Answer 128

As either low or high grade LSIL = mild dysplasia HSIL - moderate and severe dysplasia and carcinoma in situ

Question 129

What are the main causes of hypoglycaemia in diabetic

Answer 129

Insulin or sulphonylurea treatment Accidental or non-accidental overdose Increased activity Missed meal

Question 130

How are breast cancers staged

Answer 130

Using the Nottingham grading scale | Grades 1-3

Question 131

How does osteoporosis present

Answer 131

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)

Question 132

Which age group is most commonly affected by endometrial carcinoma

Answer 132

Peak is post-menopausal women 55-65

Question 133

What is Raynaud's phenomenon

Answer 133

Extremities becoming pale due to decreased blood flow in cold weather Caused by vasospasm

Question 134

Do all HPV infections lead to cancer

Answer 134

No | Majority will not cause any symptoms or damage.

Question 135

How do hyperglycaemia and insulin deficiency lead to glomerulosclerosis

Answer 135

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.

Question 136

Which endometrial carcinoma is classed as type 2

Answer 136

Serous endometrial carcinoma

Question 137

The majority of mutations in endometroid endometrial carcinoma act on which pathway

Answer 137

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.

Question 138

Removal of which precursor lesion will reduce future risk of invasive cancer

Answer 138

DCIS | Same cannot be said for LCIS

Question 139

Describe the appearance of nodular glomerulosclerosis (Kimmelstiel-Wilson disease)

Answer 139

Ovoid/spherical lesions Often laminated PAS-positive nodules of matrix found in the periphery of a glomerulus.

Question 140

Sorbitol accumulation in the lens has what effect

Answer 140

Cataract formation | Seen in diabetics

Question 141

How can cervical cancer be prevented

Answer 141

The HPV vaccine can prevent up to 70% of cases

Question 142

What are the most important targets of insulin

Answer 142

Striated muscle cells “beige” adipocytes are another target.

Question 143

What pressures do the carotid sinus baroreceptors respond to

Answer 143

Respond to pressures ranging from 60-180mmHg

Question 144

Describe the progression of HSILs

Answer 144

Has a high risk of progressing to cervical carcinoma

Question 145

Where is ADH released from

Answer 145

Posterior pituitary | It is stored here but made in the hypothalamus

Question 146

How does Cushing's suppress vasodilatory systems

Answer 146

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

Question 147

Mutations in which gene is commonly seen in serous endometrial carcinoma

Answer 147

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.

Question 148

List the features of nephrotic syndrome

Answer 148

``` Proteinuria >3g/day Hypoalbinaemia (<30) Oedema Hypercholesterolaemia Usually normal renal function ```

Question 149

What is meant by a mixed testicular tumour

Answer 149

Tumour is composed of >1 type of GCT | Accounts for 60% of all GCTs

Question 150

List symptoms of Cushing's

Answer 150

``` 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 ```

Question 151

Which conditions of adrenocortical hyperfunction can cause secondary systemic hypertension

Answer 151

Cushing syndrome Primary aldosteronism Congenital adrenal hyperplasia Licorice ingestion

Question 152

Describe the epidemiology of endometrial carcinoma

Answer 152

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

Question 153

List potential complications of radiotherapy

Answer 153

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

Question 154

How does behaviour contribute to obesity

Answer 154

Inactivity and not getting enough exercise Not burning off enough calories People in the UK are much less active now

Question 155

Which haplotype has the greatest risk of T1DM

Answer 155

DR3 or DR4 AND a DQ8 haplotype | 18- fold increase

Question 156

Describe the microscopic features of a testicular choriocarcinoma

Answer 156

These tumours are mainly composed of syncytiotrophoblasts and cytotrophoblasts

Question 157

What is the purpose of neoadjuvant therapy in breast cancer

Answer 157

Used to downstage cancer, reduce nodal involvement and improve surgical outcomes Can be chemotherapy, endocrine therapy or biologic therapy but not radiotherapy

Question 158

Young women are most effected by which type of breast cancer

Answer 158

Mainly have HER2+ or Triple neg | Rarely affected by luminal cancer

Question 159

How can you treat osteoporosis

Answer 159

Bisphosphonates – Inhibit osteoclastic bone resorption Denosumab – Anti-RANKL monoclonal antibody Hormone Therapy - Selective Oestrogen Receptor Modulator (SERM) or HRT

Question 160

List common causes of secondary systemic hypertension in middle aged adults (40-64)

Answer 160

Hyper aldosteronism Obstructive sleep apnoea Cushing's syndrome Phaeochromocytoma

Question 161

What are the main types of testicular sex chord stromal tumours

Answer 161

Leydig and Sertoli cell tumours | Leydig cell tumours are the most common of the 2 in children and adults

Question 162

What effect does insulin have on the liver

Answer 162

Decreases gluconeogenesis | Increased glycogen synthesis and lipogenesis

Question 163

How do you treat hypoglycaemia

Answer 163

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).

Question 164

How do you diagnose a hypo

Answer 164

Bloods: glucose, insulin, c-peptide, plasma ketones (symptomatic). If endogenous hyperinsulinism suspected – insulin, c-peptide, proinsulin, beta-hydroxybutyrate.

Question 165

How does Addison's disease affect BP

Answer 165

Lack of cortisol and aldosterone secretion reduces the BP

Question 166

How can the incretin effect be harnessed to treat T2 DM

Answer 166

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.

Question 167

PTEN mutations (tumour suppressor) have been identified in both hyperplastic lesions and the carcinoma - true or false

Answer 167

True | This suggests suggesting some of the mutations occur before it becomes cancerous

Question 168

Describe the glucose levels inside and outside of insulin dependent cells in diabetes

Answer 168

low glucose inside cell, high glucose outside cell Seen in skeletal muscle, adipose tissues, liver

Question 169

What is the main underlying cause for all diabetes complications

Answer 169

Persistent hyperglycaemia | Leads to glucotoxicity

Question 170

List the microscopic features of endometroid endometrial carcinoma

Answer 170

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%)

Question 171

Describe stage 1 cervical cancer

Answer 171

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

Question 172

Which nerve signals to the veins can lead to a drop in BP

Answer 172

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

Question 173

What happens when AQP2 fuses with the apical membrane in the kidney tubules

Answer 173

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)

Question 174

How is intermittent claudication managed

Answer 174

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

Question 175

What is metabolic syndrome

Answer 175

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.

Question 176

Crystalloids of Reinke are characteristic of which tumour type

Answer 176

Leydig cell tumours

Question 177

What is the most common subtype of germ cell tumour in the testes

Answer 177

Seminomas

Question 178

Long standing diabetes is associated with which eye diseases

Answer 178

Raised intra-ocular pressure = glaucoma Damage to the optic nerve

Question 179

What initial tests would you do in a middle aged adult with secondary systemic hypertension

Answer 179

Renin and aldosterone levels TSH Polysomnography if OSA suspected cause 24hr urinary cortisol and fractionated metanephrines if above tests inconclusive

Question 180

How do serous endometrial carcinomas develop

Answer 180

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.

Question 181

What initial tests would you do in an older adult with secondary systemic hypertension

Answer 181

``` Renal artery doppler MRA with contrast CT angiography TSH Urinalysis ```

Question 182

How does angiotensin 2 act on the blood brain barrier

Answer 182

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

Question 183

What factor affects the prevalence of diabetic neuropathy

Answer 183

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%

Question 184

What is DKA

Answer 184

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).

Question 185

Describe the epidemiology of PAD

Answer 185

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

Question 186

Describe the epidemiology of testicular yolk sac tumours

Answer 186

Prepubertal ones tend to be pure with good prognosis Most common tumour in <3yrs But post-pubertal are mixed

Question 187

List the macroscopic features of serous endometrial carcinomas

Answer 187

Large and bulky tumours (may look larger as typically occur in atrophic uteri). May have deeply invaded the myometrium.

Question 188

Endometrial adenosarcomas need to be differentiated from which other condition

Answer 188

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.

Question 189

List the pathological features of Cervical neuroendocrine tumours

Answer 189

Appears similar to small cell lung cancer but will also test positive for high-risk HPV.

Question 190

At which point does maximal carotid sinus sensitivity occur

Answer 190

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

Question 191

How can stress lead to secondary systemic hypertension

Answer 191

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

Question 192

List common symptoms of testicular cancer

Answer 192

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

Question 193

Describe the effect of TP53 mutations

Answer 193

Leads to accumulation of altered p53 proteins

Question 194

What initial tests would you do in a child/adolescent with secondary systemic hypertension

Answer 194

Urinalysis Urine culture Renal ultrasound Echo if above tests not conclusive

Question 195

What treatments may become available for endometrial cancer in the future

Answer 195

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

Question 196

How does ADH act on the renal collecting ducts to increase BP

Answer 196

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

Question 197

Gluconeogenesis is a constantly occurring process - true or false

Answer 197

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.

Question 198

Which endometrial carcinoma is classed as type 1

Answer 198

Endometroid endometrial carcinoma

Question 199

Describe the microscopic features of a Leydig cell tumour

Answer 199

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

Question 200

What are the symptoms of endometrial cancer

Answer 200

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

Question 201

Why is the transformation zone susceptible to cancer development

Answer 201

Immature squamous cells developing here which are highly susceptible to HPV infection (major cause of cervical cancer)

Question 202

How are endometrioid endometrial carcinomas managed

Answer 202

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.

Question 203

Breast cancer affects which age groups

Answer 203

Rare in women <25yrs and more common after 30

Question 204

Which part of the cervix can be seen on speculum examination

Answer 204

The ectocervix

Question 205

Which glomerular lesions are seen in diabetic nephropathy

Answer 205

Capillary basement membrane thickening Diffuse mesangial sclerosis Nodular glomerulosclerosis (Kimmelstiel-Wilson disease)

Question 206

What innervates the carotid sinus baroreceptors

Answer 206

The sinus nerve of hering | Branch of the glossopharyngeal nerve which synapses in the NTS in the medulla

Question 207

List the pathological features of Cervical adenosquamous cancer

Answer 207

Composed of a mix of malignant squamous and glandular epithelium.

Question 208

Describe stage III serous endometrial carcinoma

Answer 208

Carcinoma extends outside of the uterus but not outside the true pelvis.

Question 209

What is osteoporosis

Answer 209

A skeletal disease characterised by low bone mineral density and abnormal bone architecture, resulting in increasingly fragile bone and elevated fracture risk

Question 210

Where do most cervical cancers form

Answer 210

The transformation zone

Question 211

What are the most common sites of fracture in osteoporosis

Answer 211

vertebrae, proximal femur and distal radius

Question 212

Describe the volume independent mechanisms by which sodium retention cause high BP

Answer 212

increased vascular stiffness & increased central sympathetic outflow

Question 213

What are the risk factors for obesity

Answer 213

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

Question 214

What is the definition of obesity

Answer 214

“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

Question 215

Secondary systemic hypertension is the most common type of hypertension seen - true or false

Answer 215

False | Makes up only a small fraction (5-10%) of hypertensive cases

Question 216

ADH is first secreted into which vessel

Answer 216

inferior hypophyseal artery

Question 217

Why does serous endometrial carcinomas have a poor prognosis

Answer 217

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

Question 218

Endocrine therapy can be extended for how long

Answer 218

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

Question 219

How does endometroid endometrial carcinoma progress and spread

Answer 219

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.

Question 220

List the biochemical signs of DKA

Answer 220

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.

Question 221

Autoantibodies against islet antigens are found in most T1 diabetics - true or false

Answer 221

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

Question 222

What other diseases can HPV cause other than cervical cancer

Answer 222

Also causes other cancers such as vulvar, penile, anal, vaginal and oropharyngeal Low risk strains can cause genital warts

Question 223

Which lifestyle factors can increase the risk of cervical cancer

Answer 223

Cigarette smoking | Linked to 20% of cases

Question 224

Where does coarctation of the aorta most commonly occur

Answer 224

just distal to left subclavian artery in the arch of aorta

Question 225

Where is leptin produced

Answer 225

Fat cells

Question 226

Which biochemical factors must be monitored in HHS

Answer 226

Monitor and chart BG, osmolality and Na every 1-2hrs | Monitor fluid input and output

Question 227

How are serous endometrial carcinomas managed

Answer 227

Serous carcinomas are aggressive in nature so usually treated with chemotherapy even if there is no evidence of spread yet alongside the other treatments.

Question 228

How does Cushing's affect β-Adrenergic Receptors

Answer 228

Increases their sensitivity to catecholamines The SNS is upregulated and you get increased vascular tone This increased BP

Question 229

Obese people are at higher risk of a severe response to COVID - true or false

Answer 229

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

Question 230

What determines the prognosis of serous endometrial carcinoma

Answer 230

Highly dependent on the stage

Question 231

How does angiotensin II raise BP

Answer 231

Acts on the AT1 receptor to induce vascular contraction Stimulates aldosterone secretion Increases sodium resorption Acts on the blood brain barrier

Question 232

If blood results show low or undetectable insulin and no excess ketones what is the likely cause of the hypo

Answer 232

Non-pancreatic neoplasm | Anti-insulin receptor antibodies

Question 233

What is acute limb ischaemia

Answer 233

Sudden occlusion of vessels which threatens limb viability | Usually due to thromboembolism

Question 234

What are the subtypes of endometrial carcinoma

Answer 234

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

Question 235

What types of HPV are covered by the vaccine

Answer 235

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)

Question 236

List consequences of bisphosphonate treatment

Answer 236

Osteonecrosis of the jaw and atypical fractures are known risks

Question 237

Which symptoms of DKA are caused by osmotic disruption

Answer 237

Thirst, polyuria Dehydration Fatigue

Question 238

How is advanced cervical cancer managed

Answer 238

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.

Question 239

Describe the progression of LSILs

Answer 239

Low-grade doesn't directly progress to invasive cancer, in fact many cases will spontaneously regress. Only a small percentage move onto high-grade.

Question 240

What investigations are performed if a smear test comes back abnormal

Answer 240

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.

Question 241

How is critical limb ischaemia managed

Answer 241

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

Question 242

How does sleep deprivation and circadian disruption contribute to T2DM

Answer 242

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

Question 243

Which neurological conditions can cause secondary systemic hypertension

Answer 243

Psychogenic - brought on by stress Increased cranial pressure Sleep apnoea Acute stress, including surgery

Question 244

What are the complications of endometrial cancer treatment

Answer 244

Typical side effects of hysterectomy, chemo and radiotherapy Progesterone therapy can cause mild nausea, mild muscle cramps and weight gain

Question 245

How is advanced breast cancer managed

Answer 245

A combination of chemotherapy, endocrine therapy and biological therapy rather than surgery due to the nature of the disease

Question 246

List some of the clinical consequences of obesity

Answer 246

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

Question 247

What is the common mechanism of death from testicular cancer

Answer 247

Complications of metastasis

Question 248

Describe the macroscopic features of a testicular seminoma

Answer 248

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

Question 249

What does the AGE-RAGE complex cause in diabetics

Answer 249

Release of cytokines + growth factors. ROS generated in endothelial cells. Increased procoagulant activity on ECs + macrophages. Increased proliferation of vascular SMCs + ECM synthesis

Question 250

In the UK how many people will develop cervical cancer in their lifetime

Answer 250

Less than 1% of those with a cervix

Question 251

Protein linking by AGEs has what effects

Answer 251

Proteins cross-linked by AGEs resist digestion so they accumulate in the cells Can also reduce elasticity of vessels - type 1 collagen

Question 252

Which genes/proteins have been linked to post-menopausal osteoporosis

Answer 252

RANKL – Expressed by osteoblasts RANK – Facilitates osteoclast formation, function and differentiation OPG – Secreted by osteoblasts and inhibits the RANKL-induced activation of RANK

Question 253

What treatment is offered to carriers of the BRACA genes

Answer 253

Prophylactic mastectomy and salpingoophrectomy | Reduces mortality

Question 254

How does chronic hyperglycaemia cause oxidative stress + destruction of polyol pathways

Answer 254

Glucose metabolised into sorbitol (polyol) then fructose (uses up NADH). Less NADH means less GSH (antioxidant) and increased cellular susceptibility to oxidative stress

Question 255

List the main metabolic complications of diabetes

Answer 255

Hypoglycaemia Diabetic ketoacidosis (DKA) Hyperglycaemic Hyperosmolar Syndrome (HHS)

Question 256

Which cervical cancer precursor lesion is more common LSIL or HSIL

Answer 256

LSIL is much more common

Question 257

What is the underlying mechanism of insulin resistance in T2DM

Answer 257

Functional deficits in insulin signalling pathway

Question 258

How is invasive cervical cancer treated

Answer 258

More invasive cancers get hysterectomy and lymph node dissection (typically 1B or 2A). Locally advanced may also get radiation and chemotherapy.

Question 259

What is the average age of cervical cancer patients

Answer 259

Between 45-50

Question 260

Which ethnic groups have the most rapidly increasing rates of T2DM

Answer 260

Populations such as East Asian, South Asian, and Middle Easterns However, they do not show comparable increases in obesity

Question 261

Describe stage I serous endometrial carcinoma

Answer 261

Carcinoma is confined to the corpus uteri itself.

Question 262

Why is the slow progression of cervical cancer beneficial

Answer 262

Gives plenty time for detection and treatment

Question 263

HHS patients are at high risk of which vascular complication

Answer 263

Foot ulceration | Protect heels and perform daily foot checks.  

Question 264

What are the characteristic symptoms of Addison's disease

Answer 264

``` Weight loss- decreased appetite Abdominal pain Muscle weakness Fatigue Shaking/tremors Depression Low BP Sometimes darkening of skin - hyperpigmentation ```

Question 265

Which genetic factors are associated with T2DM

Answer 265

1st degree relatives have 5/10-fold increased risk of developing T2D vs. no FH – when matched for age and weight. There is a higher concordance rate in monozygotic twins (>90%) compared with T1D. At least 30 loci that confer minimal-modest increase in lifetime risk – most are involved in adipose tissue function, islet b-cell function and obesity

Question 266

What is the precursor lesion for endometrioid endometrial carcinoma

Answer 266

Endometrial hyperplasia | Most cancers develop on a background of this

Question 267

Describe how Advanced glycation end products (AGEs) are formed in diabetes

Answer 267

The result of a non-enzymatic reaction between glucose-derived metabolites & amino acids Form the AGE-RAGE complex AGEs can cross-link ECM proteins

Question 268

What is diabetes mellitus

Answer 268

A group of metabolic disorders sharing the common feature of hyperglycaemia caused by defects in insulin secretion, action, or most commonly, both.

Question 269

Describe treatment for a stage one non-seminoma testicular cancer

Answer 269

orchidectomy + short course of chemo and potential radiotherapy

Question 270

If blood results show low insulin and high ketones what is the likely cause of the hypo

Answer 270

Alcohol Pituitary insufficiency Addison’s

Question 271

BRACA cancers typically develop at what age

Answer 271

Over 70

Question 272

Describe the role of the hypothalamus in the control of energy balance

Answer 272

It receives input from the body about energy stores: if they are inadequate, triggers anabolic circuits(increase food intake and decrease expenditure) If they are adequate catabolic circuits Acts like a conductor

Question 273

Describe how diabetes leads to ketoacidosis

Answer 273

The insulin deficiency causes stress hormone activation which blocks any residual insulin action and stimulates glucagon release This leads to increased lipolysis so more FFAs sent to the liver They get oxidised in hepatocytes and ketone bodies are produced Also causes poor glucose utilisation, more proteolysis and glycogenolysis All lead to hyperglycaemia, glucosuria and then osmotic diuresis and electrolyte loss This causes dehydration + worsened renal function. If urinary excretion of ketones is compromised by dehydration then you get systemic metabolic ketoacidosis

Question 274

List the risk factor for hyperosmolar hyperglycaemia syndrome

Answer 274

T2 > T1DM CVS event (stroke or MI) Sepsis Medications: glucocorticoids & thiazides.

Question 275

How do you treat HHS

Answer 275

Fluid replacement - carefully! Low dose IV insulin if significant ketonaemia Prophylactic LMWH Identify and treat underlying precipitants such as sepsis

Question 276

Which afferent arteriole secretion can increase renin secretion in the kidney

Answer 276

NO, PGE2, PGI2

Question 277

What is the typical mechanism of death in cervical cancer

Answer 277

Most patients with advanced cancer die due to consequences of local invasion such as ureter obstruction, pyelonephritis and uraemia. These complications usually kill before the distant mets do.

Question 278

State the waist circumference scale for men

Answer 278

Desirable = Less than 94 cm (<37”) High = Between 94-102 cm (37”-40”) Very high = More than 102 cm (>40’’)

Question 279

Cervical cancer treatments can lead to fertility problems - true or false

Answer 279

True | radiotherapy, chemotherapy and the hysterectomy can all affect it

Question 280

List the grades of the Nottingham Score system for breast cancer

Answer 280

Grade 1 ( well differentiated) – grows in a tubular or cribiform pattern, has small uniform nuclei and a low proliferative rate Grade 2 ( moderately differentiated) – they have areas where cells grow as solid clusters or single infiltrating cells and have greater levels of nuclear polymorphism and high numbers of mitotic figures Grade 3 ( poorly differentiated) – invade as ragged nests or solid sheets of cells and have enlarged irregular nuclei. Its common to have a high proliferative rate and areas if tumour necrosis.

Question 281

List the different types of germ cell tumour of the testes

Answer 281

Seminoma, yolk sac, embryonal carcinoma, spermatocytic, teratoma, choriocarcinoma

Question 282

What are the common manifestations of diabetic nephropathy

Answer 282

Typically glomerular disease leading to proteinuria, with/without nephrotic syndrome Earliest manifestations: microalbuminuria (>30mg and <300mg/day).

Question 283

How is early or locally advanced breast cancer managed

Answer 283

Mostly with breast surgery - conservative or mastectomy May have radiotherapy if risk of recurrence or if nodal disease and unclear margins following mastectomy

Question 284

List the microscopic features of PAD

Answer 284

Atherosclerotic plaques within vasculature | Evidence of ischaemia in skeletal muscle - Inflammation, necrosis, fibrosis

Question 285

How does diabetic retinopathy present

Answer 285

Blurry vision Floaters Blindness

Question 286

List the features of pre-proliferative diabetic retinopathy

Answer 286

Cotton wool spots Dot & blot haemorrhages Abnormalities in venous calibre

Question 287

Which type of testicular cancer tends to metastasize earlier

Answer 287

Non seminoma GCTs | This is because they spread through the blood more commonly

Question 288

How does nodal involvement affect survival in breast cancer

Answer 288

In terms of 5-year survival No nodes = 70% 1-3 nodes = 35-40% 10 nodes = 10-15%

Question 289

What common complication of vascular disease is more common in diabetics

Answer 289

Gangrene of the lower extremities | 100x more common in diabetes

Question 290

What is circadian disruption

Answer 290

A misalignment between endogenous circadian rhythm and the cycle/rhythm created by individual behaviors

Question 291

What symptoms of testicular cancer metastasis may be seen on presentation

Answer 291

Cough, chest pain and haemoptysis from lung metastasis Cervical lymphadenopathy Abdominal masses and back ache from para aortic node metastasis

Question 292

Obesity is the second biggest preventable cause of cancer - true or false

Answer 292

True | It is only behind smoking

Question 293

List some of the clinical features of breast cancer

Answer 293

New lump within breast or axilla Thickening or swelling of any part of the breast Irritation or dimpling of the skin Redness or flaky skin at the nipple Discharge from the nipple inc. blood but excluding breast milk Nipple retraction or inversion Any general changes to the shape or size of the breast Any pain in the area of the breast

Question 294

Describe type 2 DM

Answer 294

Caused by a combination of peripheral resistance to insulin action & a secretory response by pancreatic b-cells that is inadequate to overcome insulin resistance (“relative insulin deficiency”) Approx. 90-95% of diabetics have T2D, and the vast majority are overweight.

Question 295

How can pregnancy cause secondary systemic hypertension

Answer 295

Release of oestrogen Pre-eclampsia - Develops during the third trimester of pregnancy and causes hypertension due to increased blood volume and tachycardia (increase CO)

Question 296

When does incidence of HPV infection peak

Answer 296

Between the ages of 20-24 | This is due to start of sexual activity

Question 297

State the waist circumference scale for women

Answer 297

Desirable = Less than 80 cm (<31”) High = Between 80-88 cm (31”-34”) Very high = More than 88 cm (>34”)

Question 298

Describe the pathogenesis of testicular germ cell tumours

Answer 298

Starts with a primordial germ cell with an acquired defect in differentiation Leads to activation of growth factor receptor signaling usually because of activating mutations in KIT receptor tyrosine kinase which then causes proliferation and creates germ cell neoplasia in situ The germ cell neoplasia in situ develops in utero and remains dormant then is activated at puberty by hormonal influences stimulating germ cell growth Reduplication of the short arm of ch12 ( isochromosome 12p) then creates the invasive tumour

Question 299

Which common management is offered to all PAD patients

Answer 299

Single antiplatelet therapy, Reduction of any modifiable risk factors Monitoring for the development of further circulatory system disease

Question 300

How does CKD cause hypertension via the sympathetic nervous system

Answer 300

The sodium retention cause by the angiotensin II secretion in turn causes overactivity of the sympathetic nervous system This stimulates renin production Renal ischemia also leads to renal afferent nerve excitation through adenosine

Question 301

Which environmental factors can contribute to the development of T1DM

Answer 301

Antecedent viral infections suspected but neither the type of virus nor how it promotes islet-specific autoimmunity is known. Seasonality – winter months have highest incidence of new diagnoses. Maternal factors and weight gain are also important factors.

Question 302

Describe the epidemiology of testicular seminomas

Answer 302

Makes up >50% of all GCTs | Most common in the 4th decade

Question 303

What type of inheritance does familial breast cancer (BRACA) usually follow

Answer 303

Autosomal dominant

Question 304

Describe the microscopic features of a Sertoli cell tumour

Answer 304

The tumour cells are arranged in distinctive trabeculae that tend to form cord like structures and tubules

Question 305

What is the most common invasive cancer of the female genital tract

Answer 305

Endometrial carcinoma

Question 306

Describe the action of ADH in the kidney tubules

Answer 306

It binds to ADH receptors in the basolateral membrane This activates adenylate cyclase which converts ATP into cAMP This in turn activates protein kinase A which allows trafficking of AQP-2 vesicles The AQP-2 fuses with the apical membrane and increases water uptake

Question 307

How does Cushing's result in endothelin release and what is the result

Answer 307

Catabolic effect of hypercortisolism promotes endothelial damage & increases vascular permeability This leads to endothelin 1 hypersecretion which causes endothelial dysfunction (associated with arterial hypertension)

Question 308

Which afferent arteriole secretion can inhibit renin secretion from the kidney

Answer 308

Endothelins

Question 309

Describe the macroscopic anatomy of the cervix

Answer 309

It connects the top of vagina and lower part of womb. | Made up of the external vaginal section called ectocervix and the internal endocervical canal

Question 310

What is the purpose of adjuvant therapy in breast cancer

Answer 310

Carried out after surgery to reduce the risk of recurrence

Question 311

Describe the microscopic features of a testicular embryonal carcinoma

Answer 311

Cells grow in alveolar or tubular patterns occasionally with papillary folds The neoplastic cells are large and anaplastic, epithelial in appearance and have prominent nucleoli within a hyperchromatic nucleus Mitotic figures, tumour giant cells, pleomorphism and indistinct borders are also all often seen in the cells Less differentiated lesions may have sheets of cells with cleft like spaces

Question 312

List risk factors for PAD

Answer 312

HTN, hyperlipidaemia, diabetes, age, male gender, evidence of CHD

Question 313

What are the main mechanisms of death in osteoporosis

Answer 313

Consequences of fractures | Hospitalisation +/- immobilisation due to treatment of fractures leads to complications such as pneumonias, PEs etc.

Question 314

Describe how insulin treatment is used in HHS

Answer 314

Start low dose IV insulin (0.05units/kg/hr) only if significant ketonaemia at presentation Or If BG falling at rate of <5mmol/hr despite adequate fluid replacement. Aim to maintain BG level 10-15mmol/L for 1st 24hrs

Question 315

What are the immediate complications of cervical cancer surgery

Answer 315

Patients can experience pain, must avoid sex and heavy lifting and may require a catheter whilst healing

Question 316

Describe the macroscopic features of a Leydig cell tumour

Answer 316

Usually <5cm and well circumscribed | Cut surface is distinctively gold brown and homogenous

Question 317

What is secondary systemic hypertension

Answer 317

A type of hypertension with an underlying and potentially reversible cause

Question 318

Can the location of the squamocolumnar junction change

Answer 318

Yes It can change slightly with age and hormone levels but in general it moves upwards into the canal with time This is known as squamous metaplasia - glandular is slowly replaced

Question 319

Which islet autoantigens are targeted by T cells in T1DM

Answer 319

Insulin (IAA) Glutamic acid decarboxylase (GAD; b-cell enzyme) and others e.g., islet-antigen 2 (IA2).

Question 320

List the typical biochemical signs of HHS

Answer 320

Hypovolaemia Hyperglycaemia (>30mmol/L; higher than DKA, median ~60) No major acidosis or ketonaemia. Hyperosmolar (osmolality >320 osmolal/kg), i.e., significant dehydration. Significant renal impairment Na+ may be raised on admission.

Question 321

Describe the metastatic pattern seen in HER2+ breast cancer

Answer 321

70% mets to bone, 45% to viscera and 30% to brain but its common to see mets in each. They have a bimodal relapse pattern with early and late peaks 10 years apart

Question 322

Describe neuropathic pain

Answer 322

Shooting/burning sensation Tingling/numbness Hyperalgesia Allodynia

Question 323

Where is ghrelin produced

Answer 323

Stomach

Question 324

How is glucose used in the muscle cells

Answer 324

Glucose is either stored as glycogen or oxidised to generate ATP

Question 325

List the common symptoms of hypothyroidism

Answer 325

``` Depression Brain fog Fatigue Muscle cramps Cold intolerance Weight gain Dry skin ```

Question 326

Co-morbidities are more common in HHS - true or false

Answer 326

True | All patients should be screened for things like vascular events or sepsis

Question 327

What is critical limb ischaemia

Answer 327

Severe occlusion of arteries in the limbs

Question 328

Where are the baroreceptors located

Answer 328

They are mechanoreceptors located in the carotid sinus and the aortic arch

Question 329

List the pathological characteristics of SIL

Answer 329

Characterised by nuclear atypia (enlargement, hyperchromia, coarse chromatin granules and variation in shape/size). Also have cytoplasmic halos which are due to perinuclear vacuoles which are created by HPV proteins.

Question 330

How does the lack of cortisol seen in Addison's disease affect BP

Answer 330

Loss of permissive actions on catecholamines - they usually enhance cardiac contractility (raise CO) and increase AV node conduction velocity (raise HR) When you have catecholamines insufficiency you get decreasing CO & HR and BP decreases

Question 331

Describe the pathogenesis of osteoporosis

Answer 331

It is a multifactorial disease due to an imbalance between osteoclast resorption and osteoblast formation of bone

Question 332

Describe how T cells become autoreactive in T1DM

Answer 332

The initial activation of these cells is thought to occur in the peri-pancreatic lymph nodes. Activated T cells travel to pancreas and cause b-cell injury. T-cell populations implicated: Th1 cells – may secrete cytokines incl. TNF, IFN-g that injure b-cells. CD8+ CTLs – kill b-cells directly.

Question 333

What controls renin release from the kidney

Answer 333

Renal perfusion pressure in afferent arteriole GFR Renal sympathetic nerve activation Secretion of various inhibitory or promoting compounds from afferent arteriole

Question 334

Why are obese people more likely to develop coronary heart disease

Answer 334

Obese individuals have hypertriglyceridemia and low HDL levels

Question 335

What can be used as a marker of b-cell function in diabetes

Answer 335

C-peptide | It is secreted in equal amounts as insulin on stimulation

Question 336

How does Cushing's affect the RAAS system

Answer 336

Glucocorticoids increases angiotensinogen which affects angiotensin II which in turn increase BP Plasma renin activity & plasma renin concentration are generally normal or suppressed -> an overall increase throughout in the system just not via renin Showed an increased pressor response to angiotensin II -> increased sensitivity to the agent

Question 337

Which people are at risk of circadian disruption

Answer 337

Shift workers Those with sleep disorders Any other conditions that restrict night-time sleep and daytime wakefulness

Question 338

What is the role of the nucleus tractus solitarius (NTS) located in medulla of brainstem

Answer 338

It modulates the activity of sympathetic and parasympathetic (vagal) neurons in the medulla This regulates the autonomic control of the heart and BP

Question 339

Which environmental factors can cause T2DM

Answer 339

Obesity - especially central or visceral Sedentary lifestyle - independent of obesity Sleep deprivation and circadian disruption

Question 340

How do you calculate osmolality

Answer 340

2[Na] + urine + glucose

Question 341

Describe the microscopic features of a testicular seminoma

Answer 341

Made of sheets of seminoma cells divided into poorly demarcated lobules by fibrous septae containing lymphocytic infiltrate Made of seminoma cells Occasionally have poorly demarcated granulomas as part of an immune reaction to the lesion

Question 342

List the features of background diabetic retinopathy

Answer 342

Microaneurysms Microhaemorrhages Hard exudates

Question 343

Describe treatment for stage 3-4 testicular cancer

Answer 343

3-4 cycles of chemo, surgery and potentially radiotherapy | Surgery also done for effected nodes/tissues

Question 344

Which gene mutations are associated with endometrioid endometrial carcinoma

Answer 344

PTEN, PI3K are the main 2 | FGF2 (growth factor) and many more

Question 345

What is the most common cause of death in diabetics

Answer 345

MI

Question 346

How does obesity negative impact resistance

Answer 346

Free fatty acids (FFAs) – inverse correlation between fasting FFAs and insulin sensitivity. Adipokines - sparse in obesity Inflammation – in response to excess nutrients; excess FFAs activate inflammasome Leads to IL-1 beta release and b-cell dysfunction Liver steatosis – high levels of FFAs cause hepatocyte steatosis

Question 347

Which conditions are Sertoli cell tumours associated with

Answer 347

Carney Complex Peutz-Jeghers syndrome Familial adenomatous polyposis 

Question 348

List the symptoms of DKA

Answer 348

``` High BG and ketones in the urine Excessive thirst Urinating more often and in larger amounts Sudden loss of weight Stomach pain and nausea Vomiting Dehydration - dry mouth, sore throat, dark eye circles Deep heavy breathing - Kussamauls Fruity breath Drowsiness and unconsciousness ```

Question 349

What proportion of patients presenting with intermittent claudication will progress to critical limb ischemia

Answer 349

Around 20%

Question 350

Hyaline arteriosclerosis is specific to DM - true or false

Answer 350

False More prevalent and severe but not specific for DM Also often seen in the elderly and those with hypertension

Question 351

How do the SIL classifications compare to the CIN classification

Answer 351

LSIL = CIN I | HSIL is CINII -CINIII

Question 352

What regulates the remodelling of bone in osteoporosis

Answer 352

Cytokines – IL-1, 6 & 11 Calcitrophic hormones – PTH, 1,25-hiydroxyvitamin D, calcitonin, oestrogen Colony-stimulating factors – stimulates monocytes to become osteoclasts

Question 353

What are the symptoms of cervical cancer

Answer 353

Often no symptoms and just picked up by screening. Vaginal bleeding that is unusual for patient (including after the menopause, after sex, or between regular periods). Changes to vaginal discharge (looking or smelling different) Pain or discomfort during sex Unexplained pain in your lower back or pelvis.

Question 354

What are the consequences of osteoporotic fractures of the hip

Answer 354

In the UK, 20% of osteoporotic hip fractures are fatal with a further 50% left with significantly reduced quality of life

Question 355

Which group are most prone to osteoporotic fractures

Answer 355

Caucasian women are the most prone to osteoporotic fractures, with the lifetime risk of a fragility fracture sitting at around 40%

Question 356

How do genetics contribute to obesity

Answer 356

Studies show that genetics contribute towards the development of obesity. However, it is very rare that genetics are the sole cause and usually mutations have a very small effect Most commonly implicated gene is MC4R - causes children to feel extremely hungry and become obese due to overeating

Question 357

Describe the pathogenesis of Her2+ cancers

Answer 357

Strongly associated with a pathway which amplifies the HER2 gene on ch 17 HER2 is a receptor kinase responsible for promoting cell differentiation and apposing apoptosis through stimulation of RAS and p-13K-akt signalling pathways

Question 358

What is the precursor lesion of cervical adenocarcinoma

Answer 358

Adenocarcinoma in situ.

Question 359

What are the 3 components of the neurohumoral regulation of energy balance

Answer 359

Peripheral system - leptin, ghrelin, insulin Central processing system - (arcuate nucleus of hypothalmus – first order neurons and second order neurons...- The efferent system (split into two pathways – anabolic and catabolic

Question 360

What is the unique metastasis feature of testicular GCTs

Answer 360

The histological cell type of distant metastasis or recurrent disease can differ from the original cell type This is because they come from pluripotent germ cells

Question 361

What is the typical triad of diabetes symptoms

Answer 361

Polydipsia Polyuria Polyphagia

Question 362

Describe the anatomy of the endometrium

Answer 362

Lines the internal cavity if the uterus. It is composed of glands embedded in a cellular stroma. Undergoes physiological and morphological changes during the menstrual cycle (in response to steroid hormones) Proliferative phase of rapid growth followed by a secretory phase where glands become active and then degeneration and shedding before cycle starts again.

Question 363

Classical manifestations of T1DM are typically seen once around 50% of b-cells have been destroyed - true or false

Answer 363

False | It is actually >90% destroyed before it presents

Question 364

How do AGEs affect LDL

Answer 364

It can trap it in large vessels reducing its efflux and contributing to cholesterol deposition in the intima, thus accelerating atherogenesis Can trap other non-glycated or interstitial proteins too

Question 365

Describe stage 2 cervical cancer

Answer 365

Carcinoma extends beyond cervix but not as far as the pelvic wall. Carcinoma involves the vagina but not lower 1/3

Question 366

How is acute limb ischaemia managed

Answer 366

Systemic anticoagulation Assess limb for viability: If viable - revascularisation via endovascular or surgical methods Not viable – Amputation required

Question 367

List commonly used measures for obesity

Answer 367

BMI Waist circumference NICE recommends using them in conjunction with each other Standard lab tests include LFT, Thyroid function tests and fasting glucose and HbA1c More specific tests if specific cause suspected - e.g. 24-hour urinary free-cortisol test is needed only when Cushing syndrome is suspected

Question 368

What is metabolic syndrome

Answer 368

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. Characterised by abnormalities of glucose and lipid metabolism coupled with hypertension and evidence of a systemic pro-inflammatory state.

Question 369

What is included in an annual diabetes exam

Answer 369

Smoking cessation, diet and lifestyle advice BP lowering - Target <140/80 mmHg; optimal <130/80 Cholesterol lowering - <5mmol/l; optimal <4mmol/l HbA1c test Eye exam Foot exam Guardian drugs to delay complications of diabetes - Aspirin, ACE-inhibitors, ARBs, statins

Question 370

Which other cancers, beside breast, do BRACA mutations increase the risk of

Answer 370

Ovarian - mainly BRACA 1 Prostate Pancreatic

Question 371

How does ADH cause vasoconstriction

Answer 371

Binds to V1 receptors on vascular smooth muscle to cause vasoconstriction through IP3 signal transduction & Rho-kinase pathway (protein kinase C) This mobilizes intracellular calcium stored in ER to cause vasoconstriction Overall increase arterial pressure

Question 372

How does hyperthyroidism cause hypertension

Answer 372

Causes an increase in expression of myocardial sarcoplasmic reticulum calcium-dependent ATP + A decrease in the expression of its inhibitor phospholamban This increases heart rate & cardiac contractility - CO increases by 250%

Question 373

Which type of adipocytes accumulate in obesity

Answer 373

Beige | Not white

Question 374

What is the primary effect of aldosterone

Answer 374

Increase the number of open sodium channels in luminal membrane of the principal cells in cortical collecting tubule of the kidney This causes increased sodium resorption and therefore increased sodium & water retention

Question 375

Describe the effect of Hexosamine pathways + fructose-6-phosphate generation seen in diabetes

Answer 375

Hyperglycaemia induces a flux of glycolytic intermediates via hexosamine pathway These cause cell damage and enhance oxidative stress

Question 376

Give examples of bisphosphonates

Answer 376

alendronic acid, risedronate sodium, ibandronic acid

Question 377

What is the prognosis of endometrial stromal tumours

Answer 377

5-year survival for low grade is 50% and is lower for the higher grades

Question 378

What is happening to the prevalence of T2DM

Answer 378

It is increasing due to the increasing rates of obesity | Occurring more often in children and young people

Question 379

Describe the prognosis of cervical cancer

Answer 379

Prognosis depends on the stage and subtype. For superficial carcinoma 5-year survival is 100%. Drops to less than 20% if the cancer spreads outside the pelvis.

Question 380

What facilitates glucose uptake into the pancreas and what is the effect

Answer 380

GLUT2 (insulin-independent) glucose transporters Occurs in the pancreatic b cells This uptake increases intracellular Ca2+ which stimulates insulin secretion

Question 381

What is the most common type of invasive breast cancer

Answer 381

Adenocarcinoma

Question 382

Which cells does HPV enter

Answer 382

HPV enters immature basal epithelial cells. Large number in transformation zone which is why it is so vulnerable Other areas include squamous cell trauma and repair (as virus can access the basal cells

Question 383

How do you diagnose osteoporosis

Answer 383

Duel-energy X-ray Absorptiometry (DXA) – Taken at the hip to correlate with T-score, but may be less predictive of fracture risk at other sites Bone biopsy can be taken to differentiate between osteoporosis and osteomalacia as these can be difficult to distinguish clinically

Question 384

How does the lack of aldosterone seen in Addison's disease affect BP

Answer 384

Aldosterone affects sodium & potassium ion equilibrium and thus sodium resorption in DCT to increase blood volume If lacking it hinders kidney’s ability to filter salt and water This lowers blood volume and CO and decreases BP

Question 385

List some of the psychological features of obesity

Answer 385

attitudes to food, eating disorders such as binge eating,

Question 386

How should you replace the losses in DKA

Answer 386

0.9% NaCl 1L in 1hr, then 1L over 2hrs, 1L over 4hrs, 1L over 8hrs. If glucose falls to ~15, switch to dextrose. Give insulin Give potassium 3-5mmol/kg deficit typical, plasma K+ falls w/ treatment as K+ enters cells. Don’t add K+ to 1st bag, thereafter, add K+ according to most recent VBG result

Question 387

List secondary causes of osteoporosis

Answer 387

Many conditions can lead to it including diabetes (poor blood sugar control and insulin dependence), malabsorption, malnutrition, heavy alcohol use, CKD (impaired Ca2+ homeostasis), immobilisation

Question 388

List the macroscopic features of osteoporosis

Answer 388

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

Question 389

Once a patient has recovered from a hypo (BG returned >4 mmol/L what further treatment is requires

Answer 389

Long-acting CHO (slice of toast).

Question 390

Describe the pathogenesis of luminal breast cancers

Answer 390

Due to ER positivity oestrogen exposure is their main driver Oestrogen increases several growth factors for epithelial cells and regulates the genes for epithelial cells within the breast and therefore plays a role in this cancers development Once there is a clonal population of ER + mutated cells further oestrogen exposure enhances transformation from a precursor lesion to fully malignant cells

Question 391

What is Conn's syndrome

Answer 391

Primary aldosteronism | An endocrine disorder characterized by excessive secretion of the hormone aldosterone from adrenal glands

Question 392

What is the fundamental cause of obesity

Answer 392

a chronic imbalance between calories consumed and calories expended

Question 393

What is the most common type of cancer in the breast

Answer 393

Adenocarcinoma | About 1/3 can be further classified into special histological types

Question 394

What type of epithelium covers the ectocervix

Answer 394

Mature squamous epithelium | It extends up to the external os and is continuous with vaginal walls

Question 395

Describe the stages of T1DM development

Answer 395

Stage 1 – those at risk for T1D have 100% functional b-cell mass. They will have developed 2 or more autoantibodies but are still normoglycemic and pre-symptomatic. Stage 2 – increasingly worse glucose tolerance due to progressive loss of b-cell mass; no frank symptoms. Stage 3 – classic manifestations of disease seen, this is typically once >90% of b-cells have been destroyed

Question 396

Which cancers are obese patients more susceptible to

Answer 396

lymphoma, leukemia, melanoma and multiple myeloma, and carcinomas of the esophagus, stomach, colon, gallbladder, thyroid, prostate, breast and endometrium

Question 397

How does diabetic neuropathy lead to ulcer formation

Answer 397

Loss of pain sensation can result in formation of cutaneous ulcers which heal poorly due to microvascular disease

Question 398

Which people are most at risk of HHS

Answer 398

Older people | Younger individuals in non-Caucasian group.

Question 399

List examples of peripheral vascular diseases

Answer 399

Chronic venous insufficiency -> Varicose veins, venous ulcers Thrombosis e.g. DVT Raynaud’s Phenomenon

Question 400

What molecular marker is Luminal Breast cancer positive for

Answer 400

Er positive, her 2 negative

Question 401

What difficulties do obese bodies present at autopsy

Answer 401

Physical difficulties - more sets of hands/robust equipment required to handle the larger bodies Accelerated putrefaction Quality of autopsy can suffer as difficult to position bodies for normal examinations Some conditions may be more difficult to demonstrate at autopsy than in an individual with a normal body mass index

Question 402

List examples of surgical interventions for PAD

Answer 402

thrombectomy, bypass, arterial repair

Question 403

How does Cushing's cause vasoconstriction via calcium elevation

Answer 403

Glucocorticoids downregulates the expression of Na+, Ca2+ exchanger in vascular smooth muscle cells This elevates cytosolic Ca2+ which in turn causes vasoconstriction

Question 404

Describe poorly differentiated endometroid endometrial carcinoma

Answer 404

More than 50% of the tumour is solid growth.

Question 405

Why are testicular tumours not often biopsied

Answer 405

There is a potential of seeding tumour cells | Instead orchidectomy on the presumption of malignancy is often done

Question 406

List the symptoms of autonomic neuropathy (may be seen in diabetics)

Answer 406

bladder, bowel, erectile dysfunction and postural hypotension.

Question 407

What causes widespread endothelial dysfunction in diabetics

Answer 407

Caused by persistent hyperglycaemia and insulin resistance | Feature of macrovascular disease

Question 408

How do you calculate CO

Answer 408

CO = SV x HR

Question 409

Large adenocarcinomas of the breast can invade which other structures

Answer 409

Pectoralis muscle - become fixed The skin - causing dimpling The centre of the breast - causes nipple retraction

Question 410

How does Cushing's cause secondary hypertension

Answer 410

Activation of RAAS - increase in angiotensinogen Via the mineralocorticoid activity of cortisol Enhancement of cardiovascular reactivity to vasoconstrictors Increased β-Adrenergic Receptor Sensitivity to Catecholamines Suppression of vasodilatory systems Insulin resistance & sleep apnea

Question 411

Do you still need a smear test if you have had the HPV vaccine

Answer 411

YES not all strains of HPV covered Can still get cancer

Question 412

What are the two main metabolic defects seen in T2DM

Answer 412

Insulin resistance | B-cell dysfunction

Question 413

How are testicular sex chord stromal tumours classified

Answer 413

Differentiation and histogenesis

Question 414

Which exogenous hormones can cause secondary systemic hypertension

Answer 414

Glucocorticoids Oestrogen - including pregnancy-induced and oral contraceptives Sympathomimetics and tyramine-containing foods Monoamine oxidase inhibitors

Question 415

What is the leading cause of adult blindness in the US

Answer 415

Diabetic retinopathy

Question 416

How does Cushing's result in polycythemia and what is the effect

Answer 416

Cortisol increases serum concentration of erythropoietin which has a vasoconstrictor effect It also leads to polycythemia Combined these factors increase BP

Question 417

List the pathological features of diabetic neuropathy

Answer 417

Axonal loss Axonal regeneration Demyelination (in some). Small axons affected more severely – thickening of endoneurial arterioles (increased deposition of BM material)

Question 418

Describe the structure of syncytiotrophoblasts

Answer 418

They are large multinucleated cells with abundant eosinophilic vacuolated cytoplasm containing hCG Readily detected by immunohistochemistry Seen in testicular choriocarcinomas

Question 419

Which underlying processes have been implicated in the development of diabetic neuropathy

Answer 419

Non-enzymatic protein glycation, polyol damage and diabetic microvascular disease

Question 420

Describe the structure of cytotrophoblasts

Answer 420

They are more regular and usually polygonal Have a clear cytoplasm with distinct borders. These cells have a single nucleus that is quite uniform in structure and the cells tend to grow in cords or sheets. Seen in testicular choriocarcinomas

Question 421

Describe the sex distribution of MI in diabetics

Answer 421

Occurs in men and women at the same rate

Question 422

What is renin

Answer 422

A proteolytic enzyme produced by renal juxta-glomerular cells

Question 423

How do endocrine influences cause osteoporosis

Answer 423

Oestrogen loss stimulates increased secretion of pro-inflammatory cytokines within the blood and bone marrow, leading to increased bone resorption via osteoclast recruitment and activity Seen after the menopause

Question 424

List primary causes of osteoporosis

Answer 424

Senile osteoporosis Post-menopausal Idiopathic

Question 425

Why do triple negative cancers have a poorer outcome than the others

Answer 425

No biological treatments are available

Question 426

How does insulin resistance in Cushing's cause HTN

Answer 426

The hyperinsulinemia causes increased sympathoadrenal system activity + local RAAS activation + vascular hypertrophy This all increases TPR and leads to HTN Also get sodium and water retention

Question 427

In which states does PAD become symptomatic

Answer 427

Intermittent claudication Critical limb ischaemia Acute limb ischaemia

Question 428

The most profound diabetic eye changes occur in which part of the eye

Answer 428

The retina

Question 429

Describe the microscopic features of a testicular yolk sac tumour

Answer 429

Pre and Post pubertal Tumours have the same histology Cells composing the tumours tend to be medium sized cuboidal, flattened or spindle cells arranged in a lace like pattern with less atypia than embryonal carcinoma In half of these tumours Schiller Duval Bodies are seen - capillary in the centre of a mesodermal core and both visceral and parietal layers of cells that look like primitive glomeruli Additionally eosinophilic and hyaline like globules containing AFP and a1- antitrypsin are also seen

Question 430

Which proportion of diabetics will develop retinopathy

Answer 430

60-80% of patients develop diabetic retinopathy 15-20yrs after diagnosis

Question 431

How does diabetes lead to eye disease

Answer 431

Neovascularisation due to hypoxia-induced VEGF expression of retina. DM-induced hyperglycaemia causes sorbitol formation + accumulation This causes acquired opacification of the lens (cataract).

Question 432

What is the external cervical os

Answer 432

The entrance to the endocervical canal.

Question 433

What is the action of renin

Answer 433

It cleaves plasma angiotensinogen into angiotensin I This can then be converted to angiotensin II by ACE Key to the RAAS system

Question 434

Explain how a cervical smear is carried out

Answer 434

Speculum inserted into vagina to view cervix A brush is scraped over the transformation zone and cells are smeared or spun down onto a slide Fixed, stained (Papanicolaou method) and cell structure analysed

Question 435

How can hypothyroidism cause hypertension

Answer 435

Increase in peripheral vascular resistance Causes renal dysfunction Hormonal changes can impact BP - ADH and adrenoreceptor effects Endothelial dysfunction

Question 436

What are the results of insulin resistance in T2DM

Answer 436

Failure to inhibit endogenous glucose production = high fasting BG. Failure of glucose reuptake + glycogen synthesis in skeletal muscle following a meal = high postprandial BG. Failure to inhibit activation of lipases in adipose tissue = excess triglyceride breakdown in adipocytes + high levels of circulatory FFAs.

Question 437

Why do Cushing's patients develop insulin resistance

Answer 437

The chronic glucocorticoid exposure leads to hyperinsulinemia and eventual resistance

Question 438

List the different types of diabetes mellitus

Answer 438

Type 1 Type 2 Gestational Specific types due to another cause e.g., monogenic diabetes syndromes (neonatal diabetes, maturity onset diabetes of the young [MODY]), diseases of the exocrine pancreases (e.g., CF), and drug- or chemical-induced diabetes (e.g., with glucocorticoid use, in HIV/AIDS treatment, or after organ transplantation).

Question 439

Where is glucose produced in the body

Answer 439

In the liver

Question 440

Which mutations are associated with endometrial stromal tumours

Answer 440

Several chromosomal abnormalities, particularly translocations, have been found to be specific for these malignancies (i.e., JAZF1 gets fused to SUZ12).

Question 441

Which proportion of germ cell neoplasias progress to invasive cancer

Answer 441

Around 70%

Question 442

How does hypothyroidism affect α1-adrenoreceptors and β-adrenoreceptors and what are the effects

Answer 442

Density of α1-adrenoreceptors is increased = their action is smooth muscle cell contraction, causing vasoconstriction in the blood vessels β-adrenoreceptors are reduced in vascular beds - this can induce low cardiac output, renin secretion from the kidneys, low lipolysis and anabolism in skeletal muscle

Question 443

What is the hallmark of macrovascular disease in diabetes

Answer 443

Accelerated atherosclerosis involving the aorta and large-med sized arteries

Question 444

List potential complications of Herceptin

Answer 444

neutropenia, tremors, raised or lowered BP, mild heart failure

Question 445

How does angiotensin II cause vascular contraction

Answer 445

Acts on the AT1 receptor to cause widespread vasoconstriction This increases TPR and therefore BP

Question 446

List the 4 main negative effects that glucotoxicity has on peripheral tissues

Answer 446

Advanced glycation end products (AGEs) formed PKC activation Oxidative stress + destruction of polyol pathways Hexosamine pathways + fructose-6-phosphate generation All involve an increased flux through metabolic pathways and generating harmful precursors that contribute to end-organ damage

Question 447

How does HPV replicate in the cervix

Answer 447

Replication requires the virus to move these cells out of the resting phase of the cell cycle so that the DNA synthesis mechanisms within the cell can be used to replicate the viral DNA HPV does this using the viral E6 and E7 proteins which interfere with key tumour suppressor genes such as P53 and RB.

Question 448

What effect do elevated GIP and GLP-1 have

Answer 448

This causes increased insulin secretion from b-cells, reduced glucagon secretion from a-cells and delayed gastric emptying (promotes satiety). Called the incretin effect

Question 449

How do age related changes cause osteoporosis

Answer 449

Reduced production and activity of osteoblasts leads to decreased bone formation

Question 450

List common causes of secondary systemic hypertension in young adults (19-39 y/o)

Answer 450

Thyroid dysfunction | Renal artery stenosis secondary to fibromuscular dysplasia

Question 451

Describe the natural progression of cervical cancer

Answer 451

Relatively slow progression from squamous precursor lesions to invasive carcinoma - can take decades Progression time from in-situ lesions to invasive adenocarcinoma and neuroendocrine is much shorter Will start with direct spread to nearby tissues before spreading through lymph nodes and metastasizing

Question 452

Describe the macroscopic features of a testicular spermatocytic tumour

Answer 452

Circumscribed fleshy lesions that can by myxoid potentially with cystic regions

Question 453

Where is the transformation zone of the cervix

Answer 453

In the squamocolumnar junction | It is the area where the cell types change

Question 454

Describe how amyloid deposits form in the islets in T2DM

Answer 454

Begins in and around capillaries and between cells. At advanced stages, islets can be virtually obliterated. Amyloid acts as a diffusion barrier which leads to a secretory + absorptive defect. Fibrosis may be seen too.

Question 455

What is the most common subtype of cervical carcinoma

Answer 455

Squamous cell carcinoma | Accounts for 80% of cases

Question 456

Persistent or recurrent HPV infection increases cervical cancer risk - true or false

Answer 456

True

Question 457

List symptoms of diabetes

Answer 457

``` Polydipsia Polyuria Polyphagia If severe DKA can be the presenting event Weight loss Muscle weakness Fatigue & somnolence Blurred vision Candida infection - pruritus vulvae and balanitis ```

Question 458

Which aspects of diabetes contribute to cardiovascular risk

Answer 458

Glucotoxicity - CV risk increases as HbA1c does Hypertension – found in 75% of T2 diabetics ~40% of diabetics will develop CKD which increases risk of CVD. Obesity / metabolic syndrome

Question 459

Exact cause of most testicular cancers is unknown - true or false

Answer 459

True

Question 460

How can you prevent osteoporosis

Answer 460

Achieving peak bone mass and then minimising loss of bone mass Diet supplementation with Ca2+ and vitamin D is recommended for all at risk patients Encouraging exercise, particularly resistance exercises

Question 461

What is the usual role of the BRACA genes

Answer 461

BRACA genes are tumour suppressor genes | So mutations in them leads to loss of function = cancer

Question 462

Describe the macroscopic features of a Sertoli cell tumour

Answer 462

They are firm small nodules with a gray-white to yellow homogenous cut surface

Question 463

List additional symptoms seen in advanced cervical cancer

Answer 463

Advanced cancer can cause different symptoms as it affects different organs. Haematuria, bone pain, oedema, changes to bladder/bowel habit, weight loss, loss of appetite, fatigue are just some of the symptoms you may see.

Question 464

List risk factors for breast cancer

Answer 464

Age >50 or post menopause Family Hx ( BRACA cancers ted to run in families) Previous breast lump (benign, ductal/lobular carcinoma in situ, atypical ductal hyperplasia, previous invasive carcinoma) Dense breast tissue – more cells to malfunction + makes mammography challenging High oestrogen exposure – early periods, late menopause, late/no pregnancy, HRT, contraceptive pill Obesity – post menopause will increase oestrogen levels Alcohol Radiation to chest

Question 465

What triggers insulin release

Answer 465

High levels of blood glucose

Question 466

Excessive weight and and obesity are precursors of the metabolic syndrome - true or false

Answer 466

True

Question 467

What is the greatest threat to health in the developed world

Answer 467

Obesity Poor diet contributing to more disease than physical inactivity, smoking and alcohol combined! Most of the world's population live in countries where overweight and obesity kills more people than underweight

Question 468

List causes of endometrioid endometrial carcinoma

Answer 468

``` Prolonged and unopposed estrogenic stimulation of the endometrium Obesity Hypertension Diabtetes Specific gene mutations ```

Question 469

How does obesity cause endometrioid endometrial carcinoma

Answer 469

It increases synthesis of oestrogen from androgen precursors. Excess oestrogen is the major cause

Question 470

List potential complications of acromatase inhibitors

Answer 470

osteoporosis, high cholesterol

Question 471

When would you see pancreatic islets with reduced insulin content and preserved architecture

Answer 471

Recent-onset T1DM | Insulin‐deficient islets seem to be preserved in size in early stages

Question 472

Which nerve signals to the arterioles can lead to a drop in BP

Answer 472

Decrease sympathetic tone on arterioles | This caused vasodilation and so TPR decreases leading to a decrease in BP

Question 473

Describe the lipostat

Answer 473

This is an internal set point for fat content It senses the quantity of energy stores (adipose tissue) and appropriately regulates intake and expenditure - like a thermostat regulates temperature

Question 474

Are endometrial stromal tumours likely to recur

Answer 474

Yes | Around 1/2 of tumours will recur but it is hard to predict which ones will.

Question 475

List the subtypes of cervical carcinoma

Answer 475

Squamous cell carcinoma - 80% Adenocarcinoma 0 15% Rare - adenosquamous and neuroendocrine

Question 476

What is detected on a cervical smear test

Answer 476

Highly effective in detecting cervical precursor lesions (some of which will progress if not treated). Also able to detect low stage cancers which are highly curable (at that stage). Can also test for the presence of HPV DNA in the smear sample (higher sensitivity but low specificity)

Question 477

An average woman has what chance of developing breast cancer

Answer 477

Most have a 1/8 chance of developing the disease

Question 478

What are the incretins

Answer 478

They are a hormone class involved in glucose haemostasis and satiety

Question 479

Describe the behaviour of the HPV that causes HSIL

Answer 479

The HPV is more disruptive to the cell cycle so there is greater proliferation and effect on host cells. The disrupted cell cycle may become irreversible and lead to malignant phenotype

Question 480

List the symptoms of mononeuropathy (may be seen in diabetics)

Answer 480

foot-drop, wrist-drop, or isolated CN palsies

Question 481

Describe the microscopic features of a testicular teratoma

Answer 481

Huge variety of cell and tissue types possible The elements its made from can either be mature resembling adult tissue or immature resembling foetal or embryonic tissue

Question 482

What additionally symptom may be present in Leydig cell tumours

Answer 482

Gyneacomastia in adults | In children sexual precocity due to hormonal release

Question 483

List the macroscopic features of PAD

Answer 483

Evidence of gangrene or amputated digits/ limbs Arterial ulcers – ‘punched-out’ appearance, may be associated with loss of leg hair Evidence of atherosclerosis on dissection of vessels

Question 484

Most testicular cancers have which genetic abnormality

Answer 484

Most have an isochromosome 12p | Except prepubertal teratomas and spermatocytic GCTs

Question 485

What is the leading cause of cervical cancer

Answer 485

HPV infection | Specifically the 15 strains with high oncogenic risk

Question 486

How does chronic kidney disease lead to secondary systemic hypertension

Answer 486

It damages the nephrons in the kidneys and they cannot excrete normal amounts of sodium This leads to sodium and water retention and an increase in blood volume (increase CO) There is an elevation in arterial pressure as the kidney attempts to increase renal perfusion and restore glomerular filtration This increase systemic pressure

Question 487

Describe how ADH release is triggered by changes in osmolarity

Answer 487

Osmoreceptors in hypothalamus detects ECF osmolarity If osmolarity of the plasma increases, water moves out from the osmoreceptor cells into the surrounding ECS to balance osmolarity This causes the osmoreceptor cells to depolarize and create an AP This AP causes depolarization of supraoptic nucleus cells Subsequent AP travels down hypothalamo-hypophyseal tract to depolarize the posterior pituitary gland and release ADH

Question 488

Where is PAD most commonly seen

Answer 488

most commonly in the legs

Question 489

How is the RAAS system affected by chronic kidney disease

Answer 489

Reduced blood flow in peritubular capillaries downstream of sclerosed glomeruli caused glomeruli to hypersecrete renin This increases circulating angiotensin II levels A II promotes sodium reabsorption The net loss of GFR also impairs sodium excretion so you get retention which causes HTN Fewer functioning glomeruli in CKD so need to increase GFR There is an increase arterial pressure helps bolster perfusion pressure and GFR

Question 490

What process may occur after hysterectomy

Answer 490

If ovaries removed on hysterectomy you will go through menopause after surgery. will get the normal symptoms

Question 491

What drug can be used for a T2 diabetic with CKD

Answer 491

Metformin can be used SUs and SGLT2 inhibitors are contraindicated Use a DPP-4 inhibitor but at a reduced dose.

Question 492

How does environment contribute to obesity

Answer 492

Modern environments encourage inactivity and less than healthier choices e.g. encourage cars over walking and high availability of unhealthy food choices Called the obesogenic environment

Question 493

List potential complications of tamoxifen

Answer 493

thrombosis and endometrial cancer

Question 494

Serous endometrial carcinoma usually occurs on a background of what

Answer 494

Usually occur on a background of endometrial atrophy.

Question 495

How can hypothyroidism cause endothelial dysfunction and what is the effect

Answer 495

You get downregulation of vasodilatory NO production in hypothyroidism Less dilation = higher BP

Question 496

How many fractures are caused by osteoporosis each year

Answer 496

Worldwide, osteoporosis leads to around 9 million fractures per year In 2000, fragility fractures were estimated to cost the NHS £1.8 billion and were projected to reach £2.2 billion in 2025

Question 497

What are the two classifications of diabetic retinopathy

Answer 497

non-proliferative and proliferative

Question 498

Describe the appearance of hyaline sclerosis

Answer 498

Markedly thickened arterioles

Question 499

How do you treat dehydration in HHS

Answer 499

Use 0.9% saline (±K) for fluid replacement WITHOUT insulin The fluid alone will reduce BG which will reduce osmolality Rehydrate slowly over 48hrs

Question 500

What is intermittent claudication

Answer 500

Inadequate blood flow during exercise

Question 501

What is the the most common presenting complaint for diabetic retinopathy

Answer 501

Distal symmetrical polyneuropathy of lower extremities Will then progress to upper extremities = “glove and stocking” distribution

Question 502

The proinflammatory state in metabolic syndrome is caused by what

Answer 502

It seems to be caused by activation of the inflammasome by free fatty acids and excess levels of lipids in cells and tissues stimulating interleukin 1 which induces inflammation.

Question 503

Describe the structure of a seminoma cell

Answer 503

Classically they are round or polyhedral The cytoplasm is either clear or has a watery appearance and may contain glycogen which can vary in its amount. The nucleus tends to be large and central and may have 1-2 prominent nucleoli. The cell membrane is usually distinct.

Question 504

List endocrine causes of secondary systemic hypertension

Answer 504

``` Adrenocortical hyperfunction Exogenous hormones Pheochromocytoma Acromegaly Hyperthyroidism (thyrotoxicosis) Pregnancy-induced (preeclampsia) ```

Question 505

Can cervical cancer be screened for

Answer 505

Yes | Can screen for cervical cancer and its precursors using smear or Pap tests.

Question 506

Chronic hyperglycaemia in diabetes has what effect on insulin independent tissues

Answer 506

Causes glucose to accumulate in the tissues Includes blood vessels, nerves, kidneys, eyes, CNS

Question 507

What are the downstream effects of PKC activation in chronic hyperglycaemia

Answer 507

Production of VEGF, TGF-B, and procoagulant PAI-1 by vascular endothelium These molecules are involved in angiogenesis & BM matrix Contributes to microangiopathy

Question 508

Define hypoglycaemia

Answer 508

Plasma glucose <3mmol/L

Question 509

What are adipokines

Answer 509

Adipose cytokines | Normally released in response to altered fat metabolism, incl. leptin & adiponectin (role in lowering BG)

Question 510

Describe stage 3 cervical cancer

Answer 510

Carcinoma has extended to the pelvic wall. On rectal examination there is no cancer-free space between the tumour and pelvic wall. The tumour involves the lower 1/3 of vagina

Question 511

List some of the common side effects of chemo/radiotherapy

Answer 511

Dry or broken skin, pain, tiredness, hair loss and nausea. | Many more

Question 512

Where is insulin produced

Answer 512

Pancreas

Question 513

How does endometrioid endometrial carcinoma develop from the precursor lesion

Answer 513

A stepwise accumulation of genetic mutations in tumour suppressor genes and oncogenes which leads to cancer

Question 514

Which conditions are Leydig cell tumours associated with

Answer 514

Klinefelters Cryptorchidism hereditary leiomyomatosis Renal cell carcinoma syndrome

Question 515

What is metabolic syndrome

Answer 515

Metabolic syndrome = obesity + hyperglycaemia + raised serum cholesterol and triglycerides

Question 516

Describe the epidemiology of testicular embryonal carcinomas

Answer 516

Peaks between 20-30yrs Can be mixed or pure form Tend to be more aggressive

Question 517

Describe type 1 DM

Answer 517

An autoimmune disease characterised by pancreatic b-cell destruction & an absolute deficiency of insulin Accounts for ~5-10% of diabetes and is the most common subtype diagnosed in patients <20

Question 518

What effect does insulin have on the adipose tissue

Answer 518

Increases glucose uptake, lipogenesis | Decreases lipolysis

Question 519

Which type of pain is typically caused by diabetic neuropathy

Answer 519

Neuropathic

Question 520

Early stage testicular cancer may be managed with what single treatment

Answer 520

orchidectomy alone

Question 521

Are most testicular sex chord stromal tumours benign or malignant

Answer 521

Most are benign | Only 10% are malignant

Question 522

Describe moderately differentiated endometroid endometrial carcinoma

Answer 522

Well formed glands mixed with areas of solid cell sheets (these sheets make up 50% or less of tumour)

Question 523

Why has the death rate of cervical cancer fallen

Answer 523

Mostly due to the cervical screening programme

Question 524

Describe the mechanisms of death from PAD

Answer 524

Patients diagnosed with PAD are 3-6x more likely to die from a cardiac cause than the general population Critical limb ischaemia – 5 yr mortality is around 50% May lead to sepsis from infected gangrene or ulcers Amputation as a result of PAD is associated with significant disability and mortality

Question 525

Which serum biomarkers are produced in testicular cancer

Answer 525

Lactate dehydrogenase – is proportionate to tumour AFP and HCG Elevated in 80% of non seminomatous GCTs. Only 15% of seminomatous GCTs will produce HCG.

Question 526

How does critical limb ischaemia present

Answer 526

Limb pain at rest which may wake patients from sleep | May lead to ulcers and gangrene in affected limb

Question 527

How does intermittent claudication present

Answer 527

Pain on exertion which resolves with rest

Question 528

Describe the behaviour of the HPV that causes LSIL

Answer 528

Caused by HPV infections with lots of viral replication but little effect on host cells.

Question 529

A weakened immune system can increase the risk of cervical cancer - true or false

Answer 529

True Makes it harder to fight HPV which increases risk Those with HIV are asked to get a smear every year as a result

Question 530

Name the 2 most important incretins

Answer 530

GIP GLP-1 Both are released following food ingestion

Question 531

Endometrial cancer is uncommon in which age group

Answer 531

The under 40s

Question 532

Describe the epidemiology of testicular spermatocytic tumours

Answer 532

These are rare GCT, compromising 1-2% | Affect men >65yrs

Question 533

Describe stage 0 cervical cancer

Answer 533

This is Carcinoma in Situ (CIN III or HSIL)

Question 534

List the consequences of macrovascular disease in diabetes

Answer 534

``` MI Heart failure Peripheral artery disease TIA or stroke Aortic aneurism Overt proteinuria and end-stage renal failure ```

Question 535

How do most testicular cancers spread

Answer 535

They most commonly spread through the lymphatic system firstly to retroperitoneal para aortic nodes and subsequently to mediastinal and supraclavicular nodes Haematogenous spread does occur (usually later in disease process) and is usually to lung but can also be to liver, brain and bone

Question 536

How does obesity lead to T2DM

Answer 536

Risk for diabetes increases as BMI increases. Especially caused by central or visceral obesity Highlighted by certain populations having increased rates of T2D but no comparable increase in obesity – suggests risk is related to distribution of fat not just quantity of it.

Question 537

Biological therapy is used in what type of breast cancer

Answer 537

HER2+ cancers | Used alongside surgery, chemo and radiotherapy

Question 538

What is found in the transformation zone of the cervix

Answer 538

Immature squamous cells | They develop in this region as the cell type changes

Question 539

How does coarctation of the aorta cause secondary systemic hypertension

Answer 539

Reduces distal arterial pressures and elevates arterial pressure in the head and arms This reduces systemic arterial pressure, activates RAAS and increases the blood volume

Question 540

How does ADH reach the kidney tubules

Answer 540

Travels through the bloodstream to the kidney tubules where it diffuses from plasma in peritubular capillary across into the peritubular fluid

Question 541

Does primary aldosteronism cause oedema

Answer 541

No | Pressure natriuresis and volume expansion takes over and counteracts the aldosterone induced sodium resorption

Question 542

How does obesity link to poverty

Answer 542

In Scotland there are substantial inequalities in the risk of overweight and obesity between children living in the least and most deprived areas in Scotland – and evidence to suggest that this gap is widening More common in deprived area

Question 543

What proportion of diabetes cases are linked to obesity

Answer 543

Globally, 44% of cases of diabetes are attributable to overweight and obesity The risk for type 2 diabetes rises exponentially with high BMI

Question 544

How does hypoglycaemia present

Answer 544

``` Usually rapid onset May be accompanied by odd behaviour (e.g. aggression) Sweating Dizziness Tachycardia Palpitations Seizures ``` Can progress to loss of consciousness

Question 545

Familial breast cancers make up the majority of cases - true or false

Answer 545

False | They are responsible for the minority of cancers

Question 546

What can cause Cushings

Answer 546

Adrenal causes Nonadrenal causes - pituitary adenomas Exogenous steroids

Question 547

List the typical signs and symptoms of HHS

Answer 547

Diabetes may be known, often not. High refined CHO intake pre-event. Onset is slow w/ polyuria over 2-3w + progressive dehydration.

Question 548

What factor do the baroreceptors respond to

Answer 548

Stretching of the arterial walls

Question 549

When does the incidence of HPV infection start to decline

Answer 549

From age 25 onwards | This is because women develop immunity or enter relationship

Question 550

List potential complications of HHS therapy

Answer 550

Fluid overload - cerebral oedema etc.

Question 551

How does CKD cause hypertension

Answer 551

Activation of RAAS Overactivity of the sympathetic nervous system Endothelial dysfunction (including impaired NO production), oxidative stress and elevated endothelin levels are implicated

Question 552

How does GFR affect renin release

Answer 552

If GFR is low the macula densa cells release prostaglandin E2 and nitric oxide This causes vasodilation and increased renin release

Question 553

Describe gestational DM

Answer 553

Diabetes diagnosed in the 2nd/3rd trimester of pregnancy that was not clearly overt diabetes prior to gestation.

Question 554

How can you calculate BP

Answer 554

BP = CO x TPR

Question 555

What causes testicular germ cell tumours

Answer 555

Potentially caused by environmental and genetic factors Environmental factors – in utero exposure to pesticides and nonsteroidal estrogens Genetic Factors – multiple gene loci have been located including ligand for receptor tyrosine kinases KIT and BAK, important in apoptosis and gonadal development, and variants in genes for sex hormone metabolism

Question 556

Insulin resistance predates hyperglycaemia in T2DM - true or false

Answer 556

True | It is usually accompanied by compensatory b-cell hyperfunction in the early stages

Question 557

Describe the prevalence of obesity in Scotland

Answer 557

In 2018, two thirds (65%) of adults in Scotland were overweight, including 28% who were obese

Question 558

When would you see an increase in number and size of pancreatic islets

Answer 558

This is characteristic of nondiabetic new-borns of mothers with diabetes Presumed to be a response (hyperplasia) of foetal islets to the maternal hyperglycaemia

Question 559

What determines the rate of complications from PAD

Answer 559

The size and location of the occlusion – a large femoral stenosis will require more dramatic treatment than infrapopliteal lesions

Question 560

Describe the appearance of endometrial stromal tumours

Answer 560

Stroma gives rise to neoplasms that look like normal stromal cells. Get benign stromal nodules and endometrial stromal sarcoma (low- and high-grade versions).

Question 561

What breaks down GIP and GLP-1

Answer 561

Circulating GIP and GLP-1 are degraded by enzymes called dipeptidyl peptidases (DPPs), esp. DPP-4.

Question 562

What is osteopenia

Answer 562

Decreased bone mineral density, but not to the extent of osteoporosis T-score between -1 and -2.5

Question 563

How does renal perfusion pressure affect renin release

Answer 563

A pressure decrease (due to reduced blood flow) stimulates renin release

Question 564

List the common precipitants for DKA

Answer 564

Infection Illicit drugs & alcohol Non-adherence w/ treatment Newly diagnosed diabetes.

Question 565

What is the main complication of HHS

Answer 565

Renal impairment | Therefore fluids must be prescribed carefully due to increased risk of overload

Question 566

Obesity is associated with hyperinsulinemia - true or false

Answer 566

True Due to insulin resistance significantly increase the risk of hypertension and diabetes

Question 567

Which cancer can be treated by progesterone hormone therapy

Answer 567

Some endometrial cancers

Question 568

List renal causes of secondary systemic hypertension

Answer 568

``` Acute glomerulonephritis Chronic renal disease Polycystic kidney disease Renal artery stenosis Renal vasculitis Renin-producing tumours ```

Question 569

What is the T-score and how is it relevant to osteoporosis

Answer 569

T-score – no. of SD away from the mean reference value for bone density in young, healthy adults T-score < -2.5 is classes as osteoporosis

Question 570

Is HPV common in the population

Answer 570

Yes | Around 8/10 will have it at some point and most do not cause any symptoms or damage.

Question 571

Which endometrial cancer is always classed as grade 3

Answer 571

serous endometrial carcinoma

Question 572

Describe the metastatic pattern seen in luminal breast cancer

Answer 572

Most mets go to bone (70%) Some go to viscera ( 25%) and brain (10%) They have a low rate of recurrence but long survival is possible with bone mets

Question 573

Describe the pathogenesis of sex chord stromal tumours

Answer 573

Arise due to poor gonadal development Mutations and polymorphisms create altered functioning Sertoli and Leydig cells then environmental and lifestyle factors impact development in the early years The hormonal balance is then disrupted by the dysfunctional cells creating altered germ cell differentiation resulting in the neoplasm

Question 574

List potential complications of mastectomy

Answer 574

bleeding, infection, lymphoedema, hard scar tissue formation, shoulder pain and stiffness, numbness under the arm

Question 575

Baroreceptors only respond to sudden rises in BP, not drops - true or false

Answer 575

False | They also respond to sudden reductions in arterial pressure e.g. suddenly stand up or following hemorrhage

Question 576

Describe the macroscopic features of a testicular teratoma

Answer 576

Usually 5-10cm in diameter Heterogenous appearance made of multiple tissue types and potentially have solid, cystic and cartilaginous areas All of said different cell types will be embedded in a wall of fibrous or myxoid stroma

Question 577

How can serum biomarkers be used in testicular cancer

Answer 577

In diagnosis To assess tumour burden – using lactate dehydrogenase To assess treatment response To monitor for metastasis

Question 578

How does renal sympathetic nerve activation affect renin release

Answer 578

Acts on B1 adrenergic receptor of JG cells | This increases intracellular cAMP which in turn increases renin release

Question 579

Describe how ADH release is triggered by changes in blood volume

Answer 579

If blood volume decreases then venous return does too This decreases the stretch in the atrium which represses the atrial volume receptors (firing decreases) This is picked up by the CVS centre and then the hypothalamus Stimulates ADH production

Question 580

What is the management for T2DM

Answer 580

1st line: metformin (SU if intolerant or osmotic symptoms) 2nd line: add one of: sulphonylurea (SU) OR SGLT2 inhibitor OR DPP-4 inhibitor OR thiazolidinediones (TZDs). 3rd line: add either an additional oral agent from another class OR an injectable agent (GLP-1 agonist or basal insulin).

Question 581

What is the role of insulin

Answer 581

Insulin increases rate of glucose transport into certain cells, providing a source of energy and metabolic intermediates for the biosynthesis of building blocks such as lipids, nucleotides and amino acids.

Question 582

List the pancreatic changes that may be seen in T1DM

Answer 582

Decreased number of islets - especially. in advancing disease; most of the islets are small & inconspicuous Leukocytic infiltration of the islets - can be present at any time, primarily T lymphocytes

Question 583

At which age does cervical screening start and how often do you get it

Answer 583

Invited before 25th birthday Ages 25-49 get it every 3 years 50-64 is every 5 years 65+ only get tested if 1 of last 3 tests was abnormal

Question 584

Who gets the HPV vaccine in Scotland

Answer 584

All girls and boys by ages 11-12 in Scotland. | Can pay to have it if outwith this group (i.e. missed it at school)

Question 585

Is obesity more common in men or women

Answer 585

A greater proportion of men were overweight or obese than women

Question 586

What is the main mechanism of b-cell destruction in T1DM

Answer 586

Failure of self-tolerance (in T-cells) for islet antigens | These autoreactive T cells attack islet autoantigens

Question 587

Skeletal muscle + adipose tissue make up which proportion of body weight

Answer 587

2/3

Question 588

What type of epithelium covers the endocervix

Answer 588

Columnar, mucus secreting epithelium.

Question 589

How does HPV cause cancer

Answer 589

Viral proteins interfere with tumour suppressor genes such as p53 Enhances the cell cycle and reduces the cell's ability to repair DNA damage and promotes cellular immortalization. Overall, you get increased proliferation of cells that are more likely to acquire mutations and therefore lead to cancer

Question 590

What are the consequences of vertebral osteoporotic fractures

Answer 590

significant pain and disability, and decreased life expectancy

Question 591

What causes PKC activation in chronic hyperglycaemia

Answer 591

Excessive activation due to de novo synthesis of messenger (DAG) in PKC activation process

Question 592

How do most breast cancers develop (in terms of genetics)

Answer 592

Can evolve through several pathways that allow collection of driver mutations in the epithelial cells followed by mutagenesis and an outgrowth of normal clones

Question 593

How do genetic factors cause osteoporosis

Answer 593

Rarely directly cause osteoporosis, but certain gene polymorphisms (RANK, RANKL, OPG) may lead to variation in peak bone mass All listed mutations encode osteoclast regulators

Question 594

Describe how the mineralocorticoid activity of cortisol can lead to increased BP (as seen in Cushing's)

Answer 594

Cortisol binds to both glucocorticoid & MR but MR is protected from this binding by by 11β-HSD2 (modulates corticosteroid hormone action at tissue level) However, excess cortisol as per Cushing's can exceed the protective capacity of 11β-HSD2 to inactivate the steroid to cortisone This makes it available to bind to MR where it can mimic excess aldosterone This causes sodium & water retention and increased blood volume

Question 595

What is a PAS stain

Answer 595

PAS is a staining method used to identify polysaccharides including glycogen

Question 596

Endocrine therapy is used in what type of breast cancer

Answer 596

ER+ cancers tamoxifen for for premenopausal women/men Or as acromatase inhibitors for post menopausal women

Question 597

List the mechanisms by which BP is regulated

Answer 597

Baroreceptors ADH RAAS

Question 598

How does age affect bone mass

Answer 598

Peak bone mass reached between 25-30 | After this, bone mass is lost at approximately 0.7%/year in both men and women

Question 599

Aside from retinopathy, which eye disease can occur as a result of diabetes

Answer 599

``` Central Retinal Vein Occlusion (CRVO) due to endothelial dysfunction Vitreous haemorrhage (assoc. w/ proliferative retinopathy) Ischaemic optic neuropathy (vessel occlusion). ```

Question 600

What is happening to the incidence and mortality rates from breast cancer

Answer 600

They are both rising | Now second only to lung cancer

Question 601

List the potential complications of cervical cancer surgery

Answer 601

After excisional surgery patients may have pain, bleeding, discharge changes, cervical stenosis due to scarring, infection and may experience premature birth or miscarriage. Cervix and womb removal also increases risk of lymphocysts/lymphoceles which are fluid filled swellings in the abdomen, bladder issues and lymphedema.

Question 602

What is peripheral vascular disease

Answer 602

An umbrella term covering diseases of the arteries, veins and lymphatics Primarily in the limbs, face and neck

Question 603

How do you diagnose PAD

Answer 603

Ankle-Brachial Pressure Index (ABPI) – Ratio of the systolic blood pressure in the ankle to that in the upper arm < 0.5 – Severe PAD 0.5-0.8 – Moderate PAD 0.8-1.3 – No evidence of disease >1.3 – May be falsely high reading due to calcification of arteries

Question 604

What innervates the aortic arch baroreceptors

Answer 604

The aortic nerve | Combines with the vagus nerve and travels to the NTS in the medulla

Question 605

Describe the epidemiology of testicular germ cell tumours

Answer 605

Most effect Caucasian males between ages of 15-45yrs They are the most common cancer in this demographic Their incidence is increasing for unknown reasons They are less common in African and Asian populations

Question 606

List causes of osteoporosis

Answer 606

``` Age-related changes Reduced physicals activity Genetic factors Ca2+ nutritional state Endocrine influences ```

Question 607

Describe stage IV serous endometrial carcinoma

Answer 607

Carcinoma extends out of the true pelvis or involves the mucosa of the bladder or rectum.

Question 608

Where will immature cells be found in LSIL

Answer 608

Confined to the bottom 1/3 of epithelium

Question 609

Which nerve signals to the heart can lead to a drop in BP

Answer 609

Decrease sympathetic, increase parasympathetic (vagal) tone on heart HR and contractility will decrease - this lowers CO and therefore BP

Question 610

High chromosomal instability is associated with which cancers

Answer 610

It is a feature of cancers caused by TP53 mutations

Question 611

What factor can increase the risk of mutation in luminal cancers

Answer 611

Oestrogen exposure during pregnancy and menstruation | This is because it increases breast epithelial cell proliferation and therefore increases risk

Question 612

Which genes are implicated in obesity

Answer 612

ADIPOQ - produced by fat cells and promotes energy expenditure FTO - promotes food intake Leptin - produced by fat cells Leptin receptors - when bound to leptin inhibits appetite MC4R - stimulates appetite

Question 613

Describe the epidemiology of testicular teratomas

Answer 613

Occurs at any age Adult forms make up 2-3% of GCTs They're usually mixed and malignant Infant forms are second in frequency to yolk sac tumours, tend to be pure and not assoc. with germ cell neoplasia in situ

Question 614

Which genes are responsible for the majority of familial breast cancers

Answer 614

Caused by a single gene mutation with moderate to high penetrance usually in BRACA 1 (ch 17q21) or BRACA 2 (ch 13q12.3) There are multiple different locations on these genes the mutation can occur which will effect penetrance, susceptibility to other cancers and age of onset

Question 615

Describe stage 4 cervical cancer

Answer 615

Carcinoma has extended beyond the true pelvis or has involved the mucosa of the bladder or rectum. This stage also includes those that have metastasized.

Question 616

Which ethnicities are at greater risk of developing end-stage renal disease as a consequence of diabetic nephropathy

Answer 616

Native Americans, Hispanics and African Americans Greater risk than non-Hispanic Caucasians with T2D

Question 617

Why were boys included in the HPV vaccination scheme

Answer 617

Originally given to just girls to reduce cervical cancer incidence Boys now included to reduce HPV spread and to prevent HPV cancers of the anus and oropharynx

Question 618

How does hypothyroidism affect ADH levels and what is the effect

Answer 618

Increased ADH | This leads to water retention and an increased blood volume = higher BP

Question 619

Where do most breast cancers arise

Answer 619

The terminal ductal lobular unit

Question 620

What is the ideal range for HbA1c

Answer 620

48-58mmol/mol

Question 621

Describe the metastatic pattern seen in triple negative breast cancer

Answer 621

40% mets go to bone, 35% to viscera and 25% to brain, again common to find mets in each. If they are to relapse will be in the first 8yrs ( rare after this), if they do have mets then survival is uncommon

Question 622

HHS is more common in which type of diabetes

Answer 622

T2 Higher level of portal vein insulin prevents unrestricted hepatic fatty acid oxidation and ketogenesis - glucose isn't used up that way The sustained hyperglycaemia brings chronic dehydration and leads to HHS

Question 623

List potential causes of unexpected sudden death in an obese

Answer 623

cardiomegaly, pulmonary thromboembolism, or ischemic heart disease may be the most probable diagnosis List is extensive and not limited to obesity caused disease

Question 624

What initial tests would you do in a young adult with secondary systemic hypertension

Answer 624

MRA with contrast CT angiography TSH Echo if above tests not conclusive

Question 625

Is obesity preventable

Answer 625

YES

Question 626

What is the trend in childhood obesity

Answer 626

Prevalence of children at risk of obesity has remained relatively stable - 70% are a healthy weight However, children in the UK are becoming obese at earlier ages and staying obese longer

Question 627

Do environmental factors have a role in development of T1DM

Answer 627

Yes | Must play a role since concordance rate in monozygotic twins is only ~50%.

Question 628

How does the sleep apnoea in Cushing's cause HTN

Answer 628

Increased sympathetic tone during hypoxemic episodes worsens the HTN

Question 629

What is the squamocolumnar junction

Answer 629

The meeting point of the two types of epithelium of the cervix (squamous and columnar)

Question 630

List examples of endovascular interventions for PAD

Answer 630

percutaneous transluminal angioplasty with balloon dilation, stents etc.

Question 631

Describe the series of events that occur in the baroreceptors when arterial pressure suddenly drops

Answer 631

Causes decreased baroreceptor firing This leads to disinhibition of sympathetic activity within medulla so sympathetic activity originating within rostral ventrolateral medulla increases This causes vasoconstriction (increase TPR) Tachycardia occurs to increase CO Positive inotropy -> BP increases and restored

Question 632

Describe the pathogenesis of triple negative cancers

Answer 632

These cancers tend to have tp53 mutations giving rise to inefficient cell arrest and apoptosis increasing the ability for cancerous mutations to collect

Question 633

The detection of HPV from cervical smears is not recommended in women under 30 - true or false

Answer 633

True | Not as useful in women under 30 as high incidence of infection in this age group anyway

Question 634

Aortic arch baroreceptors are less sensitive than the carotid sinus ones - true or false

Answer 634

True | They have a higher pressure threshold so are less sensitive