Pathophysiology Flashcards
Bitot spots in vitamin A deficiency
decreased differentiation of epithelial cells into specialized tissue = squamous metaplasia
describe the pathophysiological - wernickes encephalopathy in alcoholic patient given IV glucose infusion
thiamine deficiency - impaired glucose breakdown - ATP depletion worsened by glucose
how does carcinoid syndrome cause pellagra
pellagra = vitamin B3 (niacin) deficiency
tryptophan is diverted towards serotonin synthesis - niacin is derived from tryptophan
increase in what ration occurs with lactic acidosis, fasting hypoglycaemia and steatosis in alcoholism
increase in NADH/NAD due to ethanol metabolism
aspirin induced hyperthermia
aspirin increases mitochondrial permeability - decreases proton (H) gradient and increases oxygen consumption = uncoupling and hyperthermia
cataract, retinopathy and peripheral neuropathy in diabetics
lens, retina and schwann cells lack sorbitol dehydrogenase = intracellular sorbitol accumulation = osmotic damage
recurrent neissiseria bacteraemia
terminal complement deficiencies (C5-C9) = failure of MAC formation
antibodies bind to cell surface antigens = cellular destruction, inflammation and destruction
type II hypersensitivity
antigen-antibody complex = activates complement = attracts neutrophils
type III hypersensitivity
what type of hypersensitivity reaction is an acute haemolytic transfusion reaction
type II
antibody binds cell surface antigen = cellular destruction, inflammation and destruction
DiGeorge results from failure of what pharyngeal pouches to form
3rd and 4th
(3rd = inferior parathyroid + thymus, 4th = superior parathyroid + parafollicular C cells)
hyper IgM syndrome
defective CD40L on Th cells = class switching effect
leukocyte adhesion deficiency
LFA-1 integrin (CD18) defect - impaired phagocyte migration and chemotaxis
chediak-higashi syndrome
LYST mutation - microtubule dysfunction = phagocyte-leukocyte fusion defect
candida in immunodeficiency
decreased granulocytes (systemic), decreased T cells (local)
what type of hypersensitivity reaction graft vs host disease
type IV HSR, HLA mismatch - donor T cells attack host
chlamydia resistance to B lactam abx
lack of classic peptidoglycan due to reduced muramic acid
pandemic and epidemic influenza infections
pandemic; RNA segment reassortment = antigenic shift
epidemic; mutations in haemagluttin, nuraminidase = antigenic drift
prosthetic device infection by staph epidermidis
biofilm production
pseudomembranous colitis secondary to c.diff
toxin A+B damages enterocytes = watery diarrhoea
shock and DIC by gram negative bacteria
lipid A of LPS –> macrophage complement and tissue factor activation
tissue invasion by cancer
decreased E-cadherin function = decreased intracellular junction = basement membrane and ECM degredation by metaloproteinases = cell attachment to ECM = locomotion = vascular dissemination
limitless replicative potential of cancer cells
reactivation of telomerase - maintains and lengthens telomeres - prevention of chromosome shortening and lengthening
eisenmenger syndrome
uncorrected left to right shunt - increased pulmonary blood flow - remodelling of vasculature causing pulmonary HTN = RVH = right to left shunt
thoracic aortic aneurysm
cystic medial degeneration
atherosclerosis
endothelial cell dysfunction - macrophage and LDL accumulation - foam cell formation - fatty streaks - smooth muscle cell migration, extracellular matrix deposition - fibrous plaque - complex atheromas
what type of hypersensitivity reaction is rheumatic fever
type II
antibodies against M protein cross react with self antigens (molecular mimicry)
graves opthalmopathy
lymphocytic infiltration, fibroblast secretion of GAGs - increased osmotic muscle swelling and inflammation
duodenal atresia
failure to recanalize
jejunal/ileal atresia
disruption of SMA = ischaemic necrosis of feta intestine
achalasia
loss of postganglionic inhibitory neurones in myenteric plexus = loss of LES relaxation
adenoma-carcinoma sequence in colorectal cancer
loss of APC (decreased intracellular adhesion, increased proliferation) –> KRAS mutation (upregulated intracellular signalling) –> loss of tumour suppressor genes (TP53, DCC)
Reyes syndrome pathophysiology
aspirin decreases beta-oxidation by reversible inhibition of mitochondrial enzymes
alpha1 antitrypsin deficiency in the liver and lung
liver - misfold proteins aggregate in hepatocellular ER = cirrhosis
lung - uninhibited elastase in alevoli = poor compliance and panacinar emphysema
mechanism of iron overload in haemochromatosis
decreased hepcidin = increased absorption from the gut
chromosomes affected in wilsons and haemochromatosis
wilsons - 13
haemachromatosis - 6
anaemia of chronic disease
increase hepcidin = decreased release of iron from macrophages = intestinal absorption of iron
sickle cell anaemia
point mutation - substitution of glutamic acid for valine in B chain
thrombotic thrombocytopenic purpura
decreased ADAMTS13 (vWF metalloproteinase) = decreased degredation of vWF multimers = increased platelet adhesion and aggregation
achondroplasia
constitutive activation of FGFR3 = decreased chrondrocyte proliferation = decreased endochondral ossification
osteopetrosis
carbonic anhydrase II mutations = decreased ability of osteoclasts to generate acidic environment = decreased bone resorption leading to dense bones prone to fracture and decreased marrow space = pancytopenia
Rheumatoid arthritis hypersensitivity reaction
type III
SLE hypersensitivity reaction
type III
haematological manifestations are type II HSR
sjogrens hypersensitivity reaction
type IV
genetic association with atopic dermatitis
FLG gene (filaggrin)
lesion in the dominant vs non-dominant parietal cortex
dominant - grestman syndrome (acalcula, agraphia, finger agonisa, right left confusion)
non-dominant - hemispatial neglect (agonisa of contralateral side)
medial medullary syndrome
anterior spinal artery
lateral medullary syndrome
posterior inferior cerebellar artery
lateral pontine syndrome
anterior inferior cerebellar artery
intracellular eosiniophillic proteinaceous rods in hippocampus
Hirano bodies
found in alzheimers
HIV dementia
diffuse grey matter and subcortical atrophy
mutation associated with familial ALS
SOD1
spinal muscular atrophy
congenital degeneration of anterior horns SMN1 mutation –> defective snRNP assembly = LMN apoptosis
preeclampsia
abnormal placental spiral arteries –> endothelial dysfunction, vasoconstriction, ischaemia = new onset HTN and proteinuria
sarcoidosis related hypercalcaemia
non-caseating granulomas = increased macrophage activity = increased 1alpha hydroxylase activity in macrophage = vitamin D activation = increased Ca
CAG trinucleotide repeat
huntingtons disease
