Pathology - Endocrine, Environment, Nutrition

Question 1

What are the major pathological consequences of IV drug use?

Answer 1

Thrombophlebitis
Sepsis to injection site
Viral inoculation (hiv) BBV

Question 2

What are the features of IVDU endocarditis?

Answer 2

10% of hospitalised IVDU
most are staph aureus
usually associated with right sided endocarditis
can get fungi

Question 3

Describe the organ effects of lead poisoning

Answer 3

• children have a greater GI absorption and more permeable BBB, 80-85% lead accumulates in bones and teeth
• cns (more common in adults): encephalopathy, headache, dizziness
• pns (more common in children): peripheral neuropathy, wrist drop
• haem: microcytic hypochromic anaemia, hemolysis
• renal: renal tubular injury
• cvs: htn
• gu: infertility

Question 4

What are the toxic mechanisms involved in lead poisoning

Answer 4

• high affinity for sulfhydryl groups, inhibiting enzymes involved in haeme synthesis
• competes with calcium for storage in bone
• inhibits membrane associated enzymes including Na+/K+ pump

Question 5

What is sudden infant death syndrome and what risks have been identified

Answer 5

• sudden death of an infant under the age of one year which remains unexplained after investigation and autopsy
  risks: young mother, maternal smoking/drug use, deficient pre-natal care, premature, low BW, male, prone sleep

Question 6

What are the mechanisms for smoking contributing to emphysema

Answer 6

• enhances alveolar macrophage activation, leading to neutrophil recruitment
• stimulates the release of elastase from neutrophils and enhances elastase activity, leading to loss of elastic tissue
• oxidants and free radicals inactivate alpha 1 antitripsin (protease inhibitor)

Question 7

What cancers does smoking pre-dispose to

Answer 7

lung
oral
esophagus
pancreas
bladder
laryngeal, tracheal
cervix
stomach

Question 8

What are the effect of acute ionising radiation on tissues

Answer 8

• hematopoeitic stem cells are most sensitive to radiation injury
  1) sublethal: mutations, chromosome aberrations, genetic instability
  2) larger: kill proliferating cells, gut most prone, vessel endothelial cell injury
  3) even larger dose: overt tissue necrosis
  4) delayed consequences: carcinogenesis (leukemia, thyroid in children), fibrosis, dermatitis, pneumonitis

Question 9

Describe the clinical features of acute radiation syndrome

Answer 9

1) subclinical (<200 rem) = mild nausea/vomiting, lymphopenia
2) haematopoietic (200-600 rem) = nausea/vomiting, petechiae, haemorrhage, neutrophil/platelet depression
3) gastrointestinal (600-1000 rem) = nausea, vomiting, diarrhoea, severe neutrophil/platelet depression, death
4) cns (>1000 rem) = confusion, convulsions, death in 14-36 hours

Question 10

How are thermal burns classified and how do you determine extent?

Answer 10

1) superficial: confined to the epidermis
2) partial thickness: extends to the dermis
superficial dermal = epidermis and upper layer of dermis, blistering
deep dermal = extends to deeper layer of dermis
3) full thickness: involves subcutaneous tissue

measurement: TBSA not accurate, rule of nines, palm of patient = 1%

Question 11

What are the potential complications of thermal burns?

Answer 11

• early = hypovolemic shock (if >20% TBSA), compartment syndrome, airway compromise, CO poisoning
• late = infection (pseudomonas), ARDS, multi organ failure, skin grafting, psychological

Question 12

What are the consequences of thiamine deficiency

Answer 12

• dry beriberi: peripheral neuropathy with foot and wrist drop
• wet beriberi: vasodilation, AV shunting, high output cardiac failure
• wernicke’s encephalopathy: ophthalmoplegia + ataxia + confusion
• korsakoff syndrome: anterograde amnesia, retrograde amnesia, confabulation, minimal content, lack of insight

Question 13

In what areas of the CNS are lesions observed in Wernicke Korsakoff?

Answer 13

• mamillary bodies
• periventricular region of thalamus
• floor of 4th ventricle
• anterior cerebellum

Question 14

What is the function of vitamin K and what are the causes of deficiency

Answer 14

function: co-factor in hepatic carboxylation of procoagulants 2, 7, 9, 10, protein c/s
deficiency: fat malabsorption syndrome, antibiotic destruction of synthesising gut flora, neonates, liver disease

Question 15

How are pituitary adenomas classified and what clinical syndromes do they produce

Answer 15

Based on which hormone cell type they involve:

corticotroph (ACTH) = cushing syndrome
somatotroph (GH) = giantism
lactotroph (prolactin) = prolactinoma (amenorrhoea, galactorrhoea, loss of libido, infertility)
thyrotroph (TSH) = hyperthyroidism
gonadotroph (FSH/LH) = hypogonadism

Question 16

What is thyrotoxicosis, what are the causes and clinical features

Answer 16

-a hypermetabolic state due to increased T3 and T4

causes:

1) primary hyperthyroidism = graves disease, hyperfunctional multinodular goitre, hyperfunctional thyroid adenoma
2) secondary hyperthyroidism = pituitary thyrotroph adenoma, excess exogenous thyroid hormone

clinical features:

• cardiac = cardiomegaly, increased HR, palpitations, AF
• ocular = wide, staring gaze, lid lag
• neuromuscular = tremor, hyperactivity, emotional lability, insomnia
• cutaneous = flushed skin
• gastrointestinal = hypermotility
• skeletal = osteoporosis

Question 17

What is the pathogenesis and clinical findings of Graves disease

Answer 17

• most common cause of hyperthyroidism with genetic risks, type 2 hypersensitivity reaction
• autoimmune disorder caused by autoantibodies against the TSH receptor
• autoantibodies mimic the action of TSH, causing increased levels of T3/T4

clinical triad

1) hyperthyroidism = tachycardia, AF, staring gaze, tremor, emotional lability, insomnia, flushed skin
2) infiltrative ophthalmopathy = lid lag + exophthalmus + conjunctivitis
3) infiltrative dermopathy = pretibial myxedema

Question 18

What are the complications of diabetes

Answer 18

• macrovascular: atherosclerosis, MI, stroke, extremity gangrene
• microvascular: diffuse basement membrane thickening, leaky capillaries, nephropathy/retinopathy/neuropathy
• diabetic neuropathy: symmetric polyneuropathy, due to direct injury and microvascular ischaemia
• diabetic nephropathy: glomerular lesions, renal vascular lesions, pyelonephritis
• diabetic retinopathy: proliferative and nonproliferative, microaneurysms, haemorrhages, exudates, glaucoma

Question 19

Differentiate between T1DM and T2DM

Answer 19

1) T1DM (type 4 hypersensitivity reaction)
- onset in childhood, normal or under weight, HLA-D linked
- autoimmune caused by pancreatic beta cell destruction, causing absolute insulin deficiency
- high insulin levels, early insulitis

2) T2DM (type 2 hypersensitivity reaction)
- onset in adulthood, overweight, genetic concordance but not HLA linked
- not autoimmune, insulin resistance and inadequate compensation by beta cells
- low insulin levels, no insulitis

Question 20

What are the stages (pathogenesis) in the development of T1DM

Answer 20

• genetic predisposition
• precipitating event (such as viral infection)
• autoimmune destruction of islet cells (type 4 hypersensitivity reaction)
• subclinical until >90% beta cells are destroyed

Question 21

What environmental conditions may contribute to the development of T1DM

Answer 21

• Viral infections (mumps, measles, CMV, rubella) may induce tissue damage and inflammation leading to B cell antigens & autoimmune response
• Other links are weak: early childhood cow milk exposure, vitamin D deficiency, northern latitude geographic location.

Question 22

How does genetic susceptibility contribute to the development of T1DM

Answer 22

• complex pattern of genetic associations mapped on at least 20 loci
• most important is class II MHC (HLA-D) conferring 50% of total genetic susceptibility
• some non-HLA genes also linked but mechanism of association is unknown

Question 23

What are the main risks for developing T1DM?

Answer 23

• genetic factors with identical twin concordance rate of 50%
• northern european descent
• viral infections = Cocksackie B, M/M/R, CMV, EBV
• cows milk exposure prior to 4 months age
• drugs = pentamidine

Question 24

What is the pathogenesis of T2DM

Answer 24

-combination of peripheral insulin resistance and inadequate compensation by beta cells

1) insulin resistance
- decreased ability of peripheral tissues to respond to secreted insulin
- secondary to either genetic predisposition or obesity/lifestyle factors

2) beta cell dysfunction
- qualitative and quantitative, manifest as inadequate insulin secretion despite insulin resistance and high glucose
- initial beta cell hyperplasia maintains normoglycaemia with increased levels of insulin secretion, then fails
- genetic pre-disposition to beta cell failure

Question 25

What are the main risks for developing T2DM?

Answer 25

family history/genetics (not HLA linked)
obesity (most important)
physical activity
age
female: gestational diabetes, PCOS

Question 26

What is the pathogenesis of diabetic ketoacidosis

Answer 26

• complication of T1DM
• insulin deficiency and glucagon excess leading to severe hyperglycaemia, osmotic diuresis and dehydration
• activation of ketogenic pathways leading to high ketogenic amino acids and metabolic acidosis

Question 27

What are the main adverse effects of acute, severe, sustained hyperglycaemia

Answer 27

osmotic diuresis causing hypovolaemia
electrolyte loss (Na+, K+, PO4+)
hyperosmolarity

(chatgpt: osmotic diuresis with dehydration and loss of electrolytes, ketoacidosis, hyperosmolar hyperglycaemic state HHS, seizure/coma/death, infection, VTE)