Pathology - Endocrine, Environment, Nutrition Flashcards
What are the major pathological consequences of IV drug use?
Thrombophlebitis
Sepsis to injection site
Viral inoculation (hiv)
What are the features of IVDU endocarditis?
10% of hospitalised addicts
most are staph aureus
usually associated with right sided endocarditis
can get fungi
Describe the organ effects of lead poisoning
- 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
What are the toxic mechanisms involved in lead poisoning
- 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
What is sudden infant death syndrome and what risks have been identified
- 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
What are the mechanisms for smoking contributing to emphysema
- 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)
What cancers does smoking pre-dispose to
lung oral esophagus pancreas bladder laryngeal, tracheal cervix stomach
What are the effect of acute ionising radiation on tissues
- 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
Describe the clinical features of acute radiation syndrome
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
How are thermal burns classified and how do you determine extent?
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%
What are the potential complications of thermal burns?
- early = hypovolemic shock (if >20% TBSA), compartment syndrome, airway compromise, CO poisoning
- late = infection (pseudomonas), ARDS, multi organ failure, skin grafting, psychological
What are the consequences of thiamine deficiency
- 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
In what areas of the CNS are lesions observed in wernicke-korsakoff
mamillary bodies
periventicular region of thalamus
4th ventricle floor
anterior cerebellum
What is the function of vitamin K and what are the causes of deficiency
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
How are pituitary adenomas classified and what clinical syndromes do they produce
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
What is thyrotoxicosis, what are the causes and clinical features
-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
What is the pathogenesis and clinical findings of Graves disease
- 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
What are the complications of diabetes
- 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
Differentiate between T1DM and T2DM
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
What are the stages (pathogenesis) in the development of T1DM
- genetic predisposition
- precipitating event (such as viral infection)
- autoimmune destruction of islet cells (type 4 hypersensitivity reaction)
- subclinical until >90% beta cells are destroyed
What environmental conditions may contribute to the development of T1DM
infections (mumps, measles, CMV, rubella) may induce tissue damage and inflammation leading to B cell antigens
How does genetic susceptibility contribute to the development of T1DM
- 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
What are the main risks for developing T1DM
- genetic factors with identical twin concordance rate of 50%
- northern european descent
- viral infections = cocksackie b, mumps, measles, CMV, rubella, EBV
- cows milk exposure prior to 4 months age
- drugs = pentamidine
What is the pathogenesis of T2DM
-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
What are the main risks for developing T2DM
obesity (most important)
genetics (not HLA linked)
What is the pathogenesis of diabetic ketoacidosis
- 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
What are the main adverse effects of acute, severe, sustained hyperglycaemia
osmotic diuresis causing hypovolaemia
electrolyte loss (Na+, K+, PO4+)
hyperosmolarity
