Pathophysiology Flashcards
Heart Failure
Definition: a clinical syndrome in which the heart is unable to provide sufficient cardiac output to meet demand
Aetiology:
Heart related - ischaemia, valvular heart disease, myocarditis, arrhythmia
Systemic - hypertension, drug induced, amyloidosis
Risk factors - smoking, obesity, diabetes
Pathophysiology
- Underlying aetiology causes ventricular remodelling
- Eccentric or concentric hypertrophy (sarcomeres added in series or parallel)
- Leads to increased O2 demand and inability to contract sufficiently, or reduced compliance of ventricular wall
- May be fibrosis - where myocardial tissue is replaced with collagen fibres
- Macroscopically, dilated heart
- Leads to reduced stroke volume and cardiac output
Consequences - activation of compensatory mechanisms to increase blood volume and BP - further worsens demands on the heart
- Renin angiotensin aldosterone - increase blood volume
- ADH release - water retention
- Sympathetic nervous system
Clinical features
- Can be classified into left vs right heart failure, or systolic vs diastolic
Left - increased hydrostatic pressure in pulmonary vasculature leading to pulmonary oedema, reduced capacity for gas exchange leading to dyspnoea, orthopnoea
Right (from left, or as cor pulmonale due to resp disease) - congestion of systemic circulation - oedema, portal venous hypertension, ascites
Investigations
- Bloods - BNP
- ECG - features of hypertrophy
- CXR - widened mediastinum, features of pulmonary oedema
- Echo - EF, valve function etc
Acute coronary syndrome
Definition: occurs due to a mismatch between cardiac oxygen supply and demand. Commonly due to atherosclerosis of coronary arteries leading to ischaemia of myocardium
Pathophysiology of atherosclerosis
(A build up of material within the endothelium)
- Endothelial damage sheer stress or substances, eg lipids, cigarette leading to inflammation
- Inflammatory response - macrophages endocytose LDLs leading to foam cells - coalese to form fatty streaks
- Platelets adhere
- Smooth muscle forms collagen - can form a fibrous cap
- Plaque can rupture, activate clotting cascade leading to thrombus, which can embolise
- Leads to distal ischaemia and necrosis
Aetiology
- Risk factors - hypertension, hyperlipidaemia, smoking, diabetes, obesity
Clinical features - depend on degree of occlusion
- Angina - chest pain on exersion due to myocardial ischaemia, relieved at rest
ACS - due to coronary artery occlusion (unstable angina, NSTEMI or STEMI)
May be none, chest pain, breathlessness, arrhythmia, syncope
Investigations
- ECG
- Echo
- Bloods - raised cardiac enzymes
- Coronary angiogram
Asthma
Definition - chronic condition of reversible airway obstruction most commonly onset in childhood
Aetiology: multifactorial, combination of genes and environment
Precipitating factors - allergens, eg dust, pollen, cigarette smoke
Individuals are often atopic - eczema, allergic rhinitis
Pathophysiology
- Antigen presenting cells endocytose allergen and cause IgE production, which triggers histamine release from mast cells
- Histamine causes bronchoconstriction, mucous production and oedema
- Leads to breathlessness, wheeze and chest tightness
- Chronic inflammation occurs with increased eosinophil production, leading to airway remodelling
- Airways become hypersensitive and prone to spasm, leading to fibrosis and oedema with reduced elasticity
Investigations
- Lung function tests - reversibility to beta 2 agonists
FEV1/FVC <0.7 (obstructive)
Acute - peak flow
Bloods - high eosinophils, RAST (IgE to allergens)
COPD
Definition: A chronic, progressive respiratory condition of irreversible airway obstruction
Aetiology - multifactorial
- environmental exposure to cigarette smoke or industrial exposure
- can also be genetic predisposition eg alpha 1 antitrypsin deficiency
Pathophysiology
Two clinical states - emphysema and chronic bronchitis
Emphysema
- inhaled irritants - free radicals - pro inflammatory neutrophils and macrophages
- breakdown elastin in lung parenchyma and damage alveolar membranes
- leads to loss of elastic recoil and breakdown of alveolar walls leading to bullae formation
Chronic bronchitis
- inhaled irritants - excessive mucous production due to gland hypertrophy from inflammation
- bronchoconstriction due to inflammatory mediators “(muscarinic receptors)
- inflammation leading to fibrosis in bronchial wall (columnar to squamous epithelium)
- scarring and thickening leads to permanent airway narrowing
Leads to dynamic lung hyeprinflation, alveolar hypoventilation and hypercapnoea
Clinical features
- Wheeze, shortness of breath, increased work of breathing
- Cough
- chronic sputum production
- Chest hyper expansion
Investigations
- Imaging: CXR - hyper expansion, flatted diaphragm, may see bulla, CT chest
- Spirometry - reduced FEV1/FVC ratio, obstructive pattern
- Bloods - inflammatory markers if exacerbation, alpha 1 antitrypsin deficiency
Liver failure
Acute vs chronic
- Acute - medication OD (eg paracetamol), hepatitis, Wilson’s disease
- Chronic - alcohol excess, hepatitis, drug induced
- Commonly leads to inflammation —> fibrosis and change in liver architecture -Cirrhosis (irreversible) produces a patchwork of fibrotic tissue surrounding hepatic nodules containing regenerating hepatocytes - liver shrunken and nodular
Symptoms
- General non specific, fatigue, weight loss, loss of appetite
- Loss of liver function
- jaundice - increase in unconjugated bilirubin
- encephalopathy
- Coagulopathy - easy bruising, bleeding
- Low albumin
- increased oestrogen - palmar erythema, spider naive
- Portal hypertension (chronic)
- Oesophageal varices
- Ascites
- Caput medusae
- Congestive splenomegaly
Interstitial lung disease
A restrictive lung disease where the interstitial tissue of the lung is replaced by fibrous tissue
Causes:
- Primary - Idiopathic pulmonary fibrosis
- Secondary
- Connective tissue/autoimmune: sarcoidosis, rheumatoid arthritis, SLE
- Inhaled substances - asbestos, hypersensitivity pneumonitis
- Drug induced - chemotherapy, antibiotics
- Infection - pneumonia, covid
Symptoms - dyspnoea, weight loss, clubbing, worsening exercise intolerance, cough
Diagnosis
- CXR/HR CT - ground glass opacification/honeycombing
- Lung function testing - restrictive pattern (reduced TLC, normal ratio FEV1/TLC)
- Lung biopsy
Pathophysiology: gradual replacement of normal lung tissue with fibrotic tissue. Due to impairment of normal healing process
Scar tissue leads to reduction in oxygen diffusion capacity, and decreased compliance
Pneumonia
Definition: infectious process within the lung parenchyma, leading to cough, shortness of breath, fever
Risk factors - COPD, Asthma, diabetes, smoking, poor cough, cystic fibrosis
- Microorganisms enter the lungs via small aspirations
- bacteria invade the alveolar wall , triggering immune response - macrophages and neutrophils
- fluid fills the alveoli which results in impaired gas exchange
Most common - strep pneumonia, haemophilus influenzae
TB
A bacterial infection usually affecting the lungs caused by Mycobacterium tuberculosis
Active - cough, blood stained, fever, night sweats, weight losss
Can be latent
TB bacteria reach alveolar air sacks, where they replicate in macrophages. Ghon focus - primary site of infection in the lung. Forms a granuloma. Haematogenous spread can then occur to other distant sites.
Sputum sample -
Acid fast bacillus, identified by Ziehl- Neelsen stain
Consider public health measures
VTE
Obstructive disease of venous system due to a combination of factors disrupting the balance between coagulation and fibrinolytic systems
- Venous stasis - immobility
- Hypercoagulability - hereditary (factor V leiden) vs acquired (pregnancy, cancer, obesity etc)
- Endothelial damage - surgery, trauma, smoking
Thrombus - clot in situ
Embolus - intravascular material that migrates from original location
Most DVTs form in lower extremities - endothelium can be predisposed to being hypoxaemic, endothelium attract leukocytes, begin coagulation cascade, immobility worsens by reducing the skeletal muscle pump to move blood past valves
PE - leads to mechanical obstruction of pulmonary artery blood flow
- leads to dead space (alveoli ventilated but not perfused)
- if large - cardiovascular collapse due to increased pulmonary vascular resistance (decreased left ventricular filling)
Diabetes
A chronic metabolic disorder that occurs due to a lack of insulin production, or a resistance to the effect of insulin in the body
Symptoms: hyperglycaemia leading to polyuria, polydipsia, weight loss, end organ damage eg retinal damage, neuropathy, renal failure
Type 1 or Type 2
Type 1: autoimmune disease where the immune system destroys the beta cells of the pancreas which produce insulin
Genetic and environmental triggers
Commonly onset in the young
Type 2: A more gradual onset condition where there is insulin resistance
Lifestyle and genetics - increased risk in obesity, diet, lack of physical activity
Other types: eg gestational diabetes
Insulin - regulates the update of glucose from blood into cells
Diagnosis - HbA1c, fasting plasma glucose level
Pulmonary oedema
Definition: fluid build up in the alveolar spaces, impairing gas exchange, leading to shortness of breath, hypoxia and respiratory failure
Due to a change forces of hydrostatic and oncotic pressure within the lungs
Causes:
Cardiogenic - a build up of fluid due to insufficient cardiac output to maintain forward flow - increased hydrostatic pressure
- Acute heart failure/cardiogenic shock
- Chronic heart failure
- Volume overload
- Heart valve disease
- Cardiac tamponade
Non cardiogenic - due to increased microvascular permeability
- ARDS, re-expansion or negative pressure pulmonary oedema, pulmonary oedema, transfusion associated
Clinical features
- Shortness of breath
- Hypoxia
- Crackles on auscultation
Investigations
- CXR : bilateral opacification, pleural effusion, kerley B lines (thickened interlobar septa), cardiomegaly upper lobe diversion
Renal failure
Acute vs chronic decline in functional ability of the kidneys to filter waste product from the blood
Acute
Causes: pre-renal, renal, post renal
Symptoms - hyperkalaemia, uraemia, volume overload, acidosis
Chronic
Causes - diabetes, hypertension, smoking
Nephrotic syndrome, polycystic kidney disease
Symptoms - fatigue, loss of appetite, fluid overload, confusion, anaemia (due to lack of erythropoietin production)
Investigations
- Monitor of urine output
- Renal function tests, Urea, creatinine, eGFR
- FBC - anaemia
- Urine dip - blood, protein or glucose
- US: chronic renal failure - shrunken kidneys
Pathophysiology
Functional unit of the kidney is the nephron. Contains the afferent arteriole which leads to the glomerulus, where the blood is filtered across capillary walls. Surrounded by Bowmans capsule, which filtrate enters and the passes to the renal tubule. Blood leaves by the efferent arteriole.
Other cell types: Juxtaglomerular apparatus - Macula densa, mesangial cells, granular cells - adjust the filtration rate, release renin
Nephrotic syndrome - minimal change disease, membranous nephropathy
Nephritic syndrome - IgA, post streptococcal
Inflammatory bowel disease
Definition - chronic conditions, may be relapsing and remitting, which affects the GI tract due to a multifactorial combination of genetic and environmental factors
Crohn’s disease
Ulcerative colitis
Pathophysiology
- Cell mediated immune response in GI tract. Exposure to antigens causes ativation of macrophages and release of cytokines. Free radicals and other substances destroy intestinal epithelium.
Crohn’s
- Immune response transmural (Across all layers)
- Can affect any part of the GI tract
- Generation of fistulae, ulcers and abscesses
- Skip lesions
- Abdominal pain, diarrhoea, mouth ulcers, weight loss, peri-anal discomfort
UC
- Large intestine
- Superficial immune response
- Forms ulcers, tending to originate in the rectum
- Distortion of intestinal glands, goblet cell death and crypt abscess formation
- Bloody diarrhoea, abdominal pain, weight loss
Investigations
- Anaemia, iron, B12 and folate deficiency (in Crohn’s)
- Raised faecal calprotectin
- CT - dilatation, fistula formation, bowel stenosis
- Colonoscopy and biopsy
Coeliac disease
Definition - autoimmune condition triggered by gluten, a protein found in grains such as wheat and barley
Pathophysiology
- Gliadin (peptide component of gluten) resists digestion by gastric enzymes and passes into duodenum
- IgA binds and is absorbed via transferrin receptor (over expressed in coeliac disease)
- Undergoes ezyme activity via tissue transglutaminase
- Now more immunogenic and activates macrophages - HLA type more common in coeliac disease
- Immune response - pro-inflmamatory cytokines, b cells produce IgA (anti TTG, anti endomysial), T cells produce cytotoxins
- Leads to cell death - villous atrophy and crypt hyperplasia
Clinical features
- Due to malabsorption and enterocyte apoptosis
Abdominal pain, bloating and distension
Steatorrhoea
Weight loss and fatigue
Anaemia due to iron malabsorption
Osteomalacia due to calcium malabsorption
Dermatitis herpetiformis - IgA binding to tissue transglutaminase leading to blisters on the skin
Investigations
- Bloods - anaemia (iron and folate deficiency), raised anti-TTG or antiendomysial antibodies
- ODG and biopsy - villous atrophy and crypt hyperplasia, scalloping of duodenal folds
Liver cirrhosis
Definition - a late stage of hepatic fibrosis characterised by distortion of hepatic architecture, due to chronic inflammation or cholestasis.
Multiple causes of liver disease that can lead to cirrhosis
Aetiology
- Alcohol
- Viral hepatitis (B and C)
- Non alcoholic fatty liver disease
- Less common - haemochromatosis, autoimmune hepatitis
Pathophysiology
Alcohol - metabolised by cytochrome p450 enzymes, produces free radicals and acetaldehyde which causes inflammatory reaction.
Chronic hepatocellular necrosis results in activation of stellate cells, which secrete growth factors leading to collagen deposition. Produces a patchwork of fibrotic tissue surrounding hepatic nodules containing regenerating hepatocytes.
Fibrotic tissue causes compression of sinusoids impairing venous draining, leading to portal hypertension.
Clinical features
Early symptoms - non specific fatigue, weakness, loss of appetite, weight loss
Decompensated
Portal hypertension
- Ascites - fluid in peritoneal cavity
- Caput medusae, oesophageal varices
- Congestive splenomegaly
Liver failure
- Jaundice - increased unconjugated bilirubin
- Encephalopathy - increased ammonia. Asterixis, confusion, coma
- Features of impaired oestrogen metabolism - gynaecomastia, spider nave, palmar erythema
- Coagulopathy
- Low albumin
Investigations
- Bloods - raised liver function enzymes, bilirubin, coagulation abnormalities
- US - features of fibrosis - shrunken liver, irregular and nodular; ascites
- Liver biopsy
Abdominal aortic aneurysm
A degenerative process leading to weakening of the wall of the aorta with dilatation, and potentially leading to rupture
Caused by a degradation of the connective tissues of the aorta, particularly elastin, leading to loss of elasticity and progressive dilatation.
Early stage: atherosclerosis damages the endothelial lining, causing inflammatory cascade and degradation of wall
Risk factors
- Increasing age
- Male
- Hypertension
- Smoking
- Family hx
