Pathophysiology Flashcards

Question

Complement cascade

Answer 1

A series of proteins involved in the innate immune response to antigen. These exist in the serum as precursor molecules - stimuli including antigen-antibody binding, direct microbe binding or mannose-binding lectin. Common result is activation of C3, C5 and formation of the membrane attack complex. Actions are: - Formation of membrane attack complex (via the classical pathway) - Opsonisation for phagocytosis (via the alternative pathway) - Inflammation, attracting macrophages and leucocytes (via the Lectin pathway)

Answer 2

Calcium is essential to multiple body processes, including muscle contraction, nerve conduction and cardiac rhythm, and its level is tightly regulated. PTH increases serum calcium by: - Increasing conversion of Vit D to its active form in the kidney - Increasing calcium absorption in the GIT (via vitamin D) - Reducing calcium loss and increasing phosphate loss at kidney - Increasing calcium resorption from bone (via production of RANKL from osteoblasts, to increase osteoclast activity) Calcitonin - Reduces osteoclast activity - Increases phosphate retention at kidney - Increases calcium losses at kidney Vitamin D - Increases calcium absorption in GIT

Answer 3

* Heme is cleaved to biliverdin by heme oxygenase * Biliverdin is cleaved to unconjugated bilirubin by biliverdin reductase * Unconj Bilirubin is insoluble so travels in circulation bound to albumin * Alb-Bili complex enters hepatic sinusoidal blood, enters space of Disse and dissociates * Free bilirubin taken up by hepatocytes and conjugated with glucuronic acid, then secreted into bile – if biliary excretion impaired, conj bili can re-enter circulation (causing conj hyperbilirubinaemia and jaundice) * Conj bilirubin is deconj in gut into urobilinogen * 10-20% urobilinogen reabsorbed into blood and either secreted in bile or excreted in the kidney * Remainder converted to stercobilinogen and excreted in stool

Answer 4

* Formed from cholesterol by liver – initially lipid soluble * Conjugated to glycine or taurine to make them water soluble * Conjugated bile salts are actively reabsorbed in TI and colon * Bacteria deconjugate some bile salts to make them lipid soluble, which can be passively reabsorbed in gut * 90% are reabsorbed and circulated * 10% lost daily – restored by hepatic synthesis

Answer 5

Pathogenesis: excessive trypsin release overwhelms protective mechanisms and catalyses more trypsin activation, as well as other enzymes • Vascular endothelium is damaged, leading to necrosis • Dense inflammatory infiltrate worsens injury • Activated enzymes, microcirculatory impairment and inflammatory mediator release worsen damage • Not clear why some only get interstitial pancreatitis and some get necrosis

Answer 6

* Sensitisation of acinar cells to CCK-induced premature activation of zymogens * Toxic effects of alcohol metabolites such as acetaldehyde and fatty acid ethyl esters * Protein plugging in pancreatic ducts

Answer 7

Toxic effect of excessive free fatty acids in pancreatic capillaries

Answer 8

Spleen contains numerous antigen-presenting cells and T and B-cells. It is the only organ in which some bacteria (particularly encapsulated bacteria) can be effectively identified and destroyed. This is because they resist antibody binding and opsonisation in the rest of the body. In the follicle of the white pulp, infectious antigens and blood-borne pathogens are presented by antigen-presenting cells. This process initiates the activation of T-cells and B-cells, which eventually leads to the production of opsonizing antibodies (IgG). After opsonization, macrophages, dendritic cells, and neutrophils phagocytose the antigen. Asplenism therefore leads to increase risk of overwhelming sepsis, particularly secondary to encapsulated bacteria.

Answer 9

Formation of free radicals leads to DNA damage | Tumour cells lack DNA repair mechanisms and so are destroyed, whereas normal cells can repair DNA and recover

Answer 10

``` Acute effects due to: • Rapid turnover of villous epithelium • Loss of mucosal stem cells in Crypts of Lieberkuhn • Consequent mucosal denudation • Oedema and inflammation • Shortened villi • Decreased absorptive area • Followed by leukocyte infiltration • Crypt abscess formation • Ulceration ``` Occur within hours of irradiation. Should repopulate within days and symptoms should resolve within 2 weeks ``` Late effects (>3 months) are due to: • Ischaemic changes • Fibrosis and scarring in submucosa as ulcers heal • Endareritis obliterans • Spasm • Accelerated atherosclerosis ```

Answer 11

Luminal obstruction (faecolith, lymphoid hyperplasia)

Answer 12

Molecular pathogenesis of CRC has 3 main pathways (applies to both sporadic and familial) - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826728/ Chromosomal instability pathway Typified by FAP Essentially the Adenoma-Carcinoma sequence “A Krazy Disease Process” – APC, KRAS, DCC, p53 Microsatellite stable Mismatch Repair pathway Germline or sporadic mutation in DNA mismatch repair genes Typified by Lynch Abnormalities accumulate in the microsatellites in DNA – known as MSI-High - making them unstable Microsatellites = repetitive sequences of DNA throughout genome - give measure of integrity MMR mutations lead to errors in S phase and microsatellite instability Seen in 10-15% of sporadic CRC and 95% of Lynch tumours Hypermethylation/CIMP/Serrated pathway Aka Hyperplastic/Serrated Polyposis pathway Epigenetic alterations in DNA resulting in gene silencing High frequency of methylation of CpG islands – “CpG Island Methylation Phenotype” (CIMP) pathway is seen BRAF-V600 mutation and absence of KRAS mutation is usually seen MSI-H, CIMP+ BRAF+ sporadic tumours often arise from serrated polyps Can affect any gene – methylation of promoters prior to affected gene in the DNA sequence causes epigenetic silencing of that gene

Answer 13

Dilated ectactic submucosal vessels thought to be due to obstruction of smaller vessels in submucosa

Answer 14

``` Dogs are definitive host - adult tapeworms (Solices) live in GIT. They lay eggs which are passed in the dogs' stool Sheep and pigs are intermediate hosts. They eat eggs in stool, which hatch in the GIT. The larvae (oncospheres) penetrate intestinal wall and travel in the portal circulation to the liver Here they form a fluid-filled cyst called a metacestode, where protosolices develop Ingestion of infected offal containing metacestodes by dogs completes the cycle. The protosolices evaginate from the cyst and attach to the GIT mucosa, developing into adult tapeworms ```

Answer 15

V: splenic vein thrombosis, haemangiosarcoma, portal hypertension I: malaria, HIV, abscess, TB T: rupture/pseudocyst A: ITP, AHA, Sarcoid, SLE, Felty’s syndrome M: lysosomal storage disease, amyloidosis I: hypersplenism N: lymphoma, leukaemia, secondary deposit, myelofibrosis C: spherocytosis, elliptocytosis D: cyst

Answer 16

H Pylori Gram negative flagellated rod Well-adapted to survive in stomach – virulence factors include • Urease – hydrolyses gastric urea to form ammonia – alkaline barrier surrounding organism to protect it • Spiral shape and flagella help it tunnel through the mucus layer • Attaches to epithelial cells via adhesion molecules • Delivers CagA toxin into epithelial cells – these dead cells provide nutrients for H pylori • Induces gastrin hypersecretion • Not all H pylori has CagA – much more common in far east – and much more assoc with gastric ca Several mechanisms to ulcerogenesis • Increased gastrin secretion in response to meals • Reduced mucus secretion by goblet cells • Reduced bicarbonate secretion in duodenum

Answer 17

= gelatinous ascites from rupture of mucinous tumour ``` Appendiceal mucinous neoplasms (with rupture) Mucinous adenocarcinoma (appendix, colon, rectum, stomach, pancreas, urachus) Primary ovarian (contentious – may be ovarian mets from appendiceal primary) ```