Exame Flashcards
(1221 cards)
1
Q
Definição de
Saúde
A
Estado completo de bem-estar físico, mental e social.
2
Q
Classifique a afirmação como verdadeira ou falsa:
Saúde é a ausência de doença ou enfermidade.
A
Falso.
3
Q
Definição de
Mecanismos da Doença
A
Conjunto de processos bioquímicos, biológicos e fisiológicos que levam ao desenvolvimento
e progressão de uma doença.
4
Q
Tipos de
Mecanismos da Doença
A
- Etiologia
- Patogénese
- Dano molecular e celular
- Manifestação clínica
5
Q
Definição de
Etiologia
A
Causas da doença, relacionadas com fatores genéticos, infecciosos, ambientais ou com o estilo de vida.
6
Q
Definição de
Patogénese
A
Sequência de alterações moleculares, celulares e tecidulares que levam à origem da doença.
7
Q
Definição de
Manifestações clínicas
A
Sintomas e complicações resultantes da doença.
8
Q
Tipos de
Danos celulares e moleculares
A
- Inflamação
- Stress oxidativo
- Disfunção imune
- Desregulação metabólica
9
Q
Classifique a afirmação em verdadeira ou falsa:
A exposição ao ambiente pode influenciar a expressão dos genes.
A
Verdadeiro (Epigenética).
10
Q
Classifique a afirmação em verdadeira ou falsa:
As doenças congénitas são sempre resultado de fatores genéticos.
A
Falso.
A toxoplasmose é uma doença parasitária que, se for adquirida na gravidez, pode resultar na transmissão do parasita ao feto, levando à toxoplasmose congénita. Assim, esta doença congénita é causada por fatores ambientais intrauterinos.
11
Q
Causas da doença (Etiologia)
A
- Genéticas (genótipo)
- Ambientais
- Fenotípicas (genéticas + ambientais)
12
Q
Causas genéticas da doença
(Exemplos)
A
- Sexo
- Polimorfismos de nucleótido único
- Variações do número de cópias
- Inserções, deleções e translocações
- Genes modificadores da doença ou genes de suscetibilidade
13
Q
Causas ambientais da doença
(Exemplos)
A
- Fatores físicos: Sol, radiação, eletricidade som,
impacto, vibrações, pressão. - Fatores químicos: Ácidos-bases, solventes orgânicos, metais pesados, microplásticos, poluentes
- Fatores biológicos: patogéneos, toxinas, microbioma
- Estilo de vida: dieta, exercício físico, stress
14
Q
Causas epigenéticas da doença
(fatores genéticos + ambientais)
A
- Metilação do ADN
- Modificação das histonas
- Splicing de mRNA
- RNA não codificante (por exemplo, mi-RNA)
(levam a modificações nos processos de tradução transcrição e replicação do DNA e RNA)
15
Q
Definição de
Homeostase
A
Processo pelo qual os organismos vivos mantêm um ambiente interno estável, através da regulação de fatores como a temperatura, o pH e o equilíbrio de fluidos, independentemente das condições externas.
(AKA equilíbrio interno)
16
Q
Definição de
Imunidade
A
Conjunto das defesas fisiológicas pelas quais o
organismo (“hospedeiro”) distingue os seus elementos celulares de elementos estranhos.
17
Q
Funções do sistema imunitário
A
- Proteção contra microorganismos
- Isolamento/remoção de substâncias estranhas
- Vigilância imunológica
18
Q
Tipos de imunidade
A
Não específica (inata): Proteção contra elementos estranhos sem reconhecimento da sua identidade específica.
Específica (adquirida): Proteção contra elementos estranhos reconhecidos especificamente por linfócitos.
19
Q
Definição de
Imunidade não específica (inata)
A
Proteção contra elementos estranhos sem reconhecimento da sua identidade específica.
20
Q
Definição de
Imunidade específica (adquirida)
A
Proteção contra elementos estranhos reconhecidos especificamente por linfócitos.
21
Q
Imunidade não específica
Tipos de resposta
A
- Defesas nas superfícies corporais
- Inflamação
22
Q
Complete a afirmação:
Na imunidade não específica, as defesas nas superfícies corporais correspondem a uma resposta ____________, enquanto que a inflamação é uma resposta ____________.
Palavras: induzida, não induzida
A
Não induzida, induzida
23
Q
Imunidade não específica
Agentes envolvidos
A
- Leucócitos (recetores Toll-like)
- Proteínas do sistema complemento
- Interferões
24
Q
Imunidade não específica
Defesas nas superfícies corporais
A
- Pele
- Glândulas salivares e lacrimais
- Secreção mucosa epitelial (tratos respiratório e GI)
- Reflexos do espirro e tosse
- Secreção ácida gástrica
25
Causas da inflamação
* Infeção
* Trauma
* Temperatura
* Radiação
* Reação imunológica
* Lesão química
26
# Classifique a afirmação em verdadeira ou falsa:
Inflamação = Infeção
Falsa.
27
O que é **colonização** no contexto da microbiota?
É a presença de bactérias nas superfícies corporais (pele, boca, vias aéreas, cólon, vagina) sem causar doença.
28
Microbiota residente vs. microbiota transitória
A **microbiota residente** permanece no organismo por longos períodos, enquanto a **microbiota transitória** está presente temporariamente e pode ser removida por fatores ambientais ou pelo sistema imunitário.
29
# **Definição de**
Patobionte
| (Microbiota)
É um organismo comensal que pode tornar-se patogénico em determinadas condições.
30
# **Definição de**
Infeção
Invasão dos tecidos por organismos patogénicos.
31
# **Definição de**
Microbiota (Flora comensal)
Conjunto de microrganismos, principalmente bactérias, que habitam naturalmente no nosso corpo (pele, boca, vias aéreas, cólon, vagina) numa relação de comensalismo.
Ou seja, estes microorganismos coexistem no corpo humano de forma mutuamente benéfica ou neutra, sem causar danos (ou doença) ao nosso organismo.
32
# Complete a afirmação:
A inflamação pode ser classificada quanto à duração em ________, quando ocorre de forma rápida e de curta duração, e ________, quando persiste por um longo período. Quanto à dimensão, pode ser ________, quando afeta uma área específica do corpo, ou ________, quando se espalha e afeta todo o organismo.
aguda, crónica, local, sistémica
33
O que são os **sinais cardeais da inflamação**?
Os sinais cardeais da inflamação são as **manifestações clássicas da resposta inflamatória**, descritas inicialmente por Aulus Celsus (médico romano do século I d.C.) e posteriormente complementadas por Rudolf Virchow no século XIX.
34
# Classifique a afirmação em verdadeira ou falsa:
A **lesão celular e/ou necrose** são consequência de fatores como a infeção, trauma, radiação, entre outros, que desencadeiam o processo inflamatório.
Verdadeira.
35
Sinais cardeaais de inflamação de Aulius Celsus
* Dor
* Rubor (“vermelhidão”)
* Calor (aquecimento)
* Tumor (edema)
36
Qual é o quinto sinal cardeal da inflamação acrescentado por Rudolf Virchow?
Perda de função do tecido inflamado
37
Resposta inflamatória vascular
| (primeira fase)
1. **Lesão tecidular** → Gatilho inicial da inflamação.
2. **Fase isquémica transitória** → Uma breve constrição dos vasos sanguíneos ocorre imediatamente após a lesão.
3. **Formação de edema** → A **vasodilatação** aumenta o fluxo sanguíneo para a área afetada, enquanto a **venoconstrição** ajuda a direcionar esse fluxo. A **retração das junções endoteliais** permite a saída de plasma e proteínas, formando o edema.
4. **Estase sanguínea** → O sangue circula mais lentamente devido ao aumento da permeabilidade dos vasos, preparando o cenário para a migração celular.
38
Resposta inflamatória celular
| (segunda fase)
1. **Marginação** → Com a estase sanguínea, os leucócitos saem do centro do fluxo sanguíneo e aproximam-se da parede do vaso.
2. **Rolamento (“rolling”)** → Os leucócitos ligam-se temporariamente ao endotélio, formando e quebrando conexões fracas com moléculas de adesão (selectinas).
3. **Adesão** → Os leucócitos ligam-se firmemente ao endotélio através de moléculas como as integrinas.
4. **Diapedese** → Os leucócitos atravessam a parede do vaso sanguíneo, passando entre as células endoteliais.
5. **Migração (quimiotaxia)** → Os leucócitos movem-se ativamente em direção ao local da inflamação, guiados por sinais químicos (quimiocinas).
39
# **Definição de**
Necrose
Rutura da membrana plasmática e indução de inflamação pelo conteúdo expulso.
40
Tipos de necrose
* Coagulativa
* Liquefativa
* Caseosa
* Gorda (esteatonecrose)
* Fibrinóide
41
O que é a **fagocitose**?
A fagocitose é um processo pelo qual células do sistema imunitário (fagócitos, nomeadamente macrófagos) englobam e digerem micro-organismos, partículas estranhas ou restos celulares.
42
O que é a **NETose**?
A NETose é o processo de formação de armadilhas extracelulares dos neutrófilos (NETs), fibras/redes extracelulares compostas essencialmente por DNA de neutrófilos, que capturam e destroem/neutralizam agentes patogénicos.
| NET = Neutrophil Extracellular Trap
43
Quais as células responsáveis pela NETose?
Neutrófilos
| (um tipo de fagócitos)
44
Descreva o processo de fagocitose
1. Reconhecimento e ligação ao agente patogénico.
2. Englobamento/internalização do agente patogénico e formação do fagossoma (vesícula que contém o agente patogénico).
3. Fusão do fagossoma com o lisossoma (célula que contém enzimas para a digestão celular) para formação do fagolisossoma.
4. Digestão/degradação lítica do agente patogénico com enzimas, espécies reativas de oxigénio (ROS) e espécies reativas de nitrogénio (RNS).
45
Sistema complemento
Cascata enzimática que ajuda na defesa contra a infeção através da ativação de uma resposta inflamatória local.
46
# **Definição de**
Interferões
Proteínas de pequeno tamanho secretadas por células infetadas por vírus, que se ligam a recetores das próprias células e de outras células não infetadas e induzem a síntese de outras proteínas antivirais (inibição a replicação).
47
Proteínas de fase aguda negativa
* Albumina
* Transtiretina (Pré-albumina)
* Retinol binding protein
* Cortisol binding protein
* Transferrina
* Antitrombina
48
Proteínas de fase aguda positiva
* Proteína C-reativa
* Fibrinogénio
* Alfa-1-antitripsina
* Alfa-1 Glicoproteína ácida ou Orosomucóide
* Haptoglobina
* Substância Sérica Amilóide (SAA)
* Ferritina
49
# Complete a frase:
As **proteínas de fase aguda** são um grupo de proteínas cujas concentrações plasmáticas aumentam - proteínas de fase aguda ________ - ou diminuem - proteínas de fase aguda ________ - em resposta à inflamação.
positivas, negativas
50
Os 4 sinais clássicos da inflamação são edema, calor, vermelhidão e ____?
Dor
51
# Classifique a afirmação em verdadeira ou falsa:
A inflamação é um processo estereotipado, por isso faz parte da imunidade específica.
**Falsa**.
A inflamação faz parte da **imunidade inata (não específica)**, que é a resposta inicial do organismo a lesões ou infeções. A imunidade específica (ou adaptativa) envolve a produção de anticorpos e células T especializadas.
52
# Classifique a afirmação em verdadeira ou falsa:
Os principais produtores de anticorpos são as células NK.
**Falsa**.
Os principais produtores de anticorpos são os **linfócitos B**, não as células NK (Natural Killer). As células NK têm um papel importante na destruição de células infetadas ou tumorais, mas não produzem anticorpos.
53
# Classifique a afirmação em verdadeira ou falsa:
As células-memória são um tipo de linfócitos T.
**Verdadeira**.
As células-memória são um tipo de linfócitos T (ou linfócitos B), que são responsáveis por memorizar um agente patogénico após a primeira exposição, conferindo proteção a exposições futuras ao mesmo agente.
54
A resposta vascular que explica o edema é a ____ .
Vasodilatação e venoconstrição (que levam à acumulação de sangue na zona afetada).
55
# Classifique a afirmação em verdadeira ou falsa:
A **velocidade de sedimentação** dos glóbulos vermelhos permite avaliar a presença de inflamação no organismo.
Verdadeira.
56
# **Velocidade de sedimentação**
Método Westergreen vs. Centrifugação
**Método Westergreen**: baseado na observação da taxa de sedimentação dos glóbulos vermelhos numa amostra de sangue - sedimentação de forma passiva ao longo do tempo (geralmente uma hora).
**Centrifugação**: acelera o processo de sedimentação através da aplicação de uma força rotacional, demorando apenas uns minutos.
57
# Complete a frase:
Quanto maior a sedimentação de glóbulos vermelhos, ____ (maior/menor) a inflamação.
**Maior**.
A velocidade de sedimentação dos glóbulos vermelhos tende a aumentar em situações de inflamação, pois as proteínas inflamatórias (como a fibrinogénio) promovem a aglomeração dos glóbulos vermelhos, fazendo com que estes se sedimentem mais rapidamente.
58
# Complete a frase:
A proteína C-reativa é um importante marcador inflamatório e cardiovascular, que ____ (aumenta/diminui) em reposta a lesão, inflamação e infeção.
Aumenta.
59
# **Definição de**
Proteína C-Reativa
Proteína plasmática reagente de fase aguda (isto é, que está relacionada com a resposta do organismo à inflamação aguda), sintetizada pelo fígado.
60
Em que consiste a imunidade específica?
Reconhecimento de proteínas ou polissacáridos “estranhos” específicos nas membranas e paredes dos microrganismos por **linfócitos**.
61
Resposta típica da imunidade específica
1. Reconhecimento de um antigénio por linfócitos
2. Ativação dos linfócitos (ligação ao antigénio, expansão clonal)
3. Ataque lançado pelos linfócitos ativados e suas secreções
62
O que são **células NK** (Natural Killer)?
São uma classe distinta de linfócitos que reconhece e destrói diretamente células tumorais e células infetadas por vírus.
63
# Classifique a afirmação em verdadeira ou falsa:
As células NK são células da imunidade específica que são ativadas por antigénios específicos.
**Falso**.
As células NK são uma exceção da imunidade específica, uma vez que não são ativadas por antigénios específicos, nem através dos recetores MHC.
64
Linfócitos B vs. Linfócitos T
Enquanto os linfócitos B conseguem reconhecer diretamente os antigénios, os linfócitos T só reconhecem (epitopos de) antigénios expressos em recetores MHC de células apresentadoras de antigénios (APCs).
65
Resposta dos linfócitos B
Após ativados, os linfócitos B proliferam (isto é, multiplicam-se) e diferenciam-se em dois tipos de células:
* **Células plasmáticas**: São células especializadas na **produção de anticorpos**, que são libertados na corrente sanguínea, ligando-se aos antigénios para os neutralizar.
* **Células de memória**: São células de longo prazo que memorizam o antigénio que desencadeou a resposta imunitária, permitindo fornecer uma resposta rápida e eficiente se o mesmo agente patogénico voltar a infetar o organismo no futuro.
66
Funções dos anticorpos
* Neutralização de antigénios
* Estimulação da fagocitose
* Estimulação da citotoxidade das células
67
# Complete a frase:
No final do ataque dos linfócitos B, a maior parte das células ____ morre por apoptose, enquanto que as células ____ persistem.
plasmáticas, memória
68
# Complete a frase:
Os linfócitos T ____ só reconhecem antigénios incorporados em recetores MHC classe II, enquanto que os linfócitos T ____ só reconhecem antigénios incorporados em recetores MHC classe I.
helper, citotóxicos
69
# Complete a frase:
Os antigénios incorporados em recetores MHC classe I, reconhecidos pelos linfócitos T ____ , são ____ , enquanto que os antigénios incorporados em recetores MHC classe II, reconhecidos pelos linfócitos T ____ , são ____ (ou seja, sofrem um processamento).
citotóxicos, endógenos, helper, exógenos
70
Antigénios endógenos vs. exógenos
Os antigénios apresentados pelos recetores MHC classe II (reconhecidos pelos linfócitos T helper) são exógenos, ou seja, **vêm de fora da célula**, como bactérias, vírus, fungos ou partículas estranhas.
Os antigénios apresentados pelos recetores MHC classe I (reconhecidos pelos linfócitos T citotóxicos) são endógenos, ou seja, **têm origem no interior da própria célula**, incluindo proteínas normais da célula (como proteínas estruturais ou enzimáticas) e proteínas estranhas que resultam de infeções virais ou da presença de células tumorais.
71
A febre é o aumento da temperatura central do organismo, provocada pela
disfunção do __________.
**Hipotálamo**
O hipotálamo é uma estrutura do cérebro responsável por regular a temperatura corporal. Numa resposta inflamatória, certas substâncias chamadas pirogénicas **alteram o set point da temperatura no hipotálamo, causando febre**.
72
As substâncias que induzem a febre chamam-se __________.
Pirogénios
73
# Classifique a afirmação em verdadeira ou falsa:
Os granulomas são geralmente observados na fase aguda de uma inflamação.
**Falso**.
Os granulomas são estruturas típicas da **fase crónica de uma inflamação**. Estes correspondem a uma coleção organizada de macrófagos ativados (histiócitos epitelióides),
linfócitos e células gigantes (Langhans).
74
# Classifique a afirmação em verdadeira ou falsa:
O facto de um idoso estar internado num lar é um fator protetor contra o desenvolvimento de sépsis, devido à facilidade de prestação de cuidados de saúde.
**Falso**.
Embora o facto de estar internado num lar de idosos possa proporcionar cuidados médicos regulares, os idosos têm um risco elevado de desenvolver sépsis, devido à sua fragilidade imunológica, presença de doenças crónicas, e maior probabilidade de infeções resultantes. Além disso, ambientes de cuidados de saúde, como lares de idosos, podem ser locais onde infeções podem ser transmitidas facilmente. Portanto, a facilidade de cuidados não é necessariamente um fator protetor.
Assim, os idosos internados em lares apresentam os principais fatores de risco de desenvolvimento de sépsis: **imunocomprometimento**, **co-morbilidades**, **idade avançada** e **institucionalização**.
75
# Classifique a afirmação em verdadeira ou falsa:
A alteração hemodinâmica que se espera encontrar num doente com sépsis é a hipertensão.
**Falso**.
A manifestação orgânica cardiovascular da sépsis é a **hipotensão**, resultante da vasodilatação.
76
# Classifique a afirmação em verdadeira ou falsa:
A febre corresponde a uma temperatura corporal superior a 38ºC.
**Falso** (incompleto).
A febre corresponde a uma temperatura corporal superior a 38ºC, **com alteração do set-point hipotalâmico**. Na ausência desta alteração, trata-se somente de uma **hipertermia**.
77
# Classifique a afirmação em verdadeira ou falsa:
A febre surge quando há a sistematização da resposta inflamatória.
Verdadeira.
78
Distinga febre de hipertermia.
**Febre** ocorre quando o set point hipotalâmico aumenta em resposta a pirogénios, resultando numa temperatura corporal superior a 38ºC.
**Hipertermia** corresponde a uma temperatura corporal superior a 38ºC provocada por exposição ao calor, atividade física excessiva ou drogas/fármacos que alteram a regulação térmica. Neste caso, não há alteração do set point hipotalâmico.
79
Exemplos de pirogénios endógenos
IL-1, IL-6, TNF-alfa, IFN-alfa
80
Exemplos de pirogénios exógenos
Produtos microbianos (ex.: lipopolissacárido - LPS)
81
Desvantagens da febre
**Efeitos Celulares:**
* Estimula mecanismos excitatotóxicos e morte celular (ex.: morte celular direta aos 41ºC).
* Promove desnaturação proteica.
* Provoca lesão da matriz nuclear (aos 40ºC).
* Altera a síntese de ácidos nucleicos (como DNA e RNA).
* Destabiliza e danifica a membrana plasmática (através da acumulação intracelular de Na+ e Ca2+ e redução intracelular de K+).
**Efeitos Sistémicos:**
* Reduz a absorção de nutrientes.
* Favorece a translocação da flora microbiana, aumentando o risco de infeções secundárias.
* Fragilização da barreira hematoencefálica, permitindo a entrada de patogénios e toxinas no SNC.
82
3 fases da febre
1. Fase de ascensão térmica
2. Fase de estado (febril)
3. Fase de defervescência
83
# **Febre**
Manifestação clínica da **fase de ascensão térmica**
* Sensação de mal-estar, mialgias, cefaleias, anorexia, tremores
* Aumento da freq. cardíaca (7 bpm/ºC)
* Pele pálida e fria, piloereção, vermelhidão facial
* Desorientação/delírio, convulsões
84
# **Febre**
Manifestação clínica da **fase de estado (febril)**
Pele quente e húmida
85
# **Febre**
Manifestação clínica da **fase de defervescência**
* Pele quente
* Sudação abundante
86
# Classifique a afirmação em verdadeira ou falsa:
As proteínas de choque térmico estão apenas no citoplasma da célula.
**Falsa**.
Também podem estar na membrana plasmática.
87
# Complete a frase:
As proteínas de choque térmico ajudam a ________ (agregar/reconformar) proteínas desnaturadas e evitam a sua ________ (agregação/reconformação).
reconformar, agregação.
88
# Complete a frase:
Indivíduos com concentrações mais ________ (elevadas/baixas) de proteínas de choque térmico são **mais resistentes** aos efeitos prejudiciais da febre.
elevadas
89
# **Definição de**
Proteínas de choque térmico
Proteínas que ajudam a reparar e eliminar proteínas desnaturadas pelo choque térmico (febre), evitando a sua agregação e promovendo a sua reconformação.
90
Possíveis desfechos da inflamação
* **Resolução completa**
* **Cura por fibrose** (lesão considerável em que há susbtituição do parênquima do tecido por tecido fibroso)
* **Evolução para cronicidade** (agente lesivo persiste, interferindo com o processo de recuperação)
91
# **Definição de**
Inflamação crónica
Persistência de inflamação aguda por patogénios/materiais não degradáveis.
92
# **Definição de**
Granuloma
Coleção organizada de macrófagos ativados (histiócitos epitelióides), linfócitos e células gigantes (Langhans), formada em resposta a infeções por bactérias, fungos ou parasitas.
93
Quais são os principais leucócitos envolvidos na inflamação crónica?
* Monócitos
* Macrófagos
* Linfócitos
* Plasmócitos
* Fibroblastos
94
Exemplos de doenças infeciosas granulomatosas
* **Tuberculose** (infeção causada pela bactéria Mycobacterium tuberculosis)
* **Lepra** (infeção causada pelas bactérias Mycobacterium leprae ou Mycobacterium lepromatosis)
* **Criptococose** (infeção causada pela levedura/fungo encapsulada(o) Cryptococcus neoformans ou C)
95
Exemplos de doenças não infeciosas granulomatosas
* **Doença de Crohn** (doença inflamatória crónica do trato gastrointestinal)
* **Granuloma de corpo estranho** (resposta inflamatória crónica a um corpo estranho inerte, tipicamente fios de sutura ou fibras)
* **Granulomatose com poliangite** (forma de vasculite, que é uma inflamação dos vasos sanguíneos, provocada pelo próprio sistema imunológico - doença autoimune -, afetando principalmente rins e pulmões)
* **Artrite de células gigantes** (outra forma de vasculite, caracterizada pela inflamação crónica das artérias grandes e médias da cabeça, pescoço e parte superior do corpo)
96
# **Léxico médico**
Qual é o sufixo comum associado à inflamação?
-ite
97
# **Definição de**
Sépsis
Estado patológico caracterizado por lesão orgânica secundária a uma resposta inflamatória descontrolada a uma infeção.
98
Fatores de risco da sépsis
* Imunocomprometimento
* Co-morbilidades (ex.: diabetes)
* Idade jovem (< 1 ano) e idade avançada (> 75 anos)
* Institucionalização (polimedicação, dispositivos médicos)
99
Etiologia (causas) da Sépsis
A sépsis é geralmente causada pelos seguintes patogénios:
* Bactérias (Gram +, Gram -)
* Fungos, vírus, parasitas (raros)
100
Quais as principais **infeções primárias** que antecedem a sépsis (secundária)?
* Respiratórias
* Genitourinárias
* Gastrointestinais
* Cutâneas
101
Manifestações clínicas **gerais** da sépsis
* Edema generalizado
* Febre
* Taquicardia (frequência cardíaca superior ao normal)
* Taquipneia (respiração rápida e superficial)
* Estado geral de saúde reservado
102
Fisiopatologia (fases) da sépsis
1. **Ativação sistémica de mediadores locais** (sistema complemento, citocinas, mastócitos, macrófagos)
2. **Vasodilatação e disrupção endotelial** generalizadas
3. **Edema generalizado**
4. **Hipovolémia intravascular** (diminuição do volume de sangue)
1. **Coagulação intravascular** disseminada
2. **Trombose microvascular**
5. **Isquémia tecidular** (redução do fluxo sanguíneo nos tecidos, que leva à disfunção orgânica)
103
# **Manifestações clínicas orgânicas da sépsis**
Sistema Nervoso Central
Alteração do estado mental
104
Manifestações clínicas: orgânicas vs. gerais
As manifestações clínicas **gerais** afetam **todo o organismo no geral**, enquanto que as manifestações clínicas **orgânicas** afetam **um órgão ou sistema em específico**.
105
# Classifique a afirmação em verdadeira ou falsa:
As coagulopatias são uma das manifestações clínicas da sépsis.
Verdadeira.
106
# **Manifestações clínicas orgânicas da sépsis**
Sistema cardiovascular
Hipotensão (devido à taquicardia e hipovolémia intravascular)
107
# **Manifestações clínicas orgânicas da sépsis**
Sistema respiratório
Dificuldade respiratória aguda (devido à taquipneia)
108
# **Manifestações clínicas orgânicas da sépsis**
Fígado
Icterícia (a pele e a parte branca do olho ficam amareladas)
109
# **Manifestações clínicas orgânicas da sépsis**
Rins
Oligúria (diminuição da quantidade de urina)
110
O que é um **choque séptico**?
Ocorre quando a sépsis provoca uma pressão arterial perigosamente baixa (**hipotensão grave**).
111
No choque séptico, a pele inicialmente fica ________ (quente/fria), enquanto que no final a pele se torna ________ (quente/fria) e cianótica.
quente, fria
## Footnote
NOTA: cianótica = azulada
112
# **Definition:**
Neoplasia
**Abnormal and uncontrolled growth of cells**, typically as a consequence of alterations of the cellular function, which can be benign or malign.
113
# **True or False:**
Neoplasia results in solid tumors.
**False.**
Neoplasia might result in the formation of tumors, but **not all neoplasia result in solid tumors**, such as hematological cancers.
114
# **Distinguish:**
Benign vs. Malign neoplasia
* **Benign neoplasia**: the cells grow slower and are contained in the origin tissue or organ, as they are unable ti metastasize;
* **Malign neoplasia**: the cells grow quickly and are able to metastasize, invading other tissues and/or organs besides their origin.
115
# **Truth or False:**
Neoplasia and Cancer are synonyms.
**False.**
Neoplasia is an abnormal and uncontrolled growth of cells, which can be benign or malign. A malign neoplasia can also be called Cancer.
116
# **Definition:**
Tumor
"Mass-effect" or space-occupying lesion resultant from an increase of a certain tissue or region. In other words, it is a solid mass made resultant from increased cell growth.
117
# **True or False:**
Neoplasia may not always lead to solid tumors, but tumors are always a result of neoplasia.
**False.**
It is true that neoplasia does not always lead to the formation of solid tumors (for example, in the case of hematological cancers). But tumors can also be a consequence of **inflammatory reactions or fluid accumulation**, which means they aren't only a consequence of neoplasia.
118
# **List:**
Neoplasia risk factors
* Environmental factors
* Inherit genetics
* Age
* Gender
* Ethnicity and race
* Viruses, parasites and bacteria
* Complications from previous pathologies and/or commorbities
119
# **Examples:**
Environmental risk factors of Neoplasia
* Raditation exposure (such as ionizing radiation, which can damage DNA);
* Chemical exposure (such as arsenic, asbestos, etc.);
* Tobacco and exhaustion gases;
* Alcohol (since it is decomposed into acetaldeyde in the body, which damages DNA).
120
# **True or False:**
Cancer can be passed through generations.
**False.**
Cancer itself cannot be passed between generations, but **genetic alterations** associated with a **higher predisposition** to develop cancer can be passed down.
121
# **Question:**
Why is **age** a risk factor of Neoplasia?
With aging:
* The immune system becomes weaker and less efficient;
* There is an increase of genomic instability;
* There is a cumulative effect of life-long exposure to environmental factors, viral infections, etc.
122
# **Question:**
Why is **gender** a risk factor of Neoplasia?
* Societal behaviours, habits and lifestyle;
* Hormonal differences;
* Anatomical differences;
* Occupational jobs.
123
# **Question:**
Why are **ethnicity and race** risk factors of Neoplasia?
* Inherent genetic factors;
* Different lifestyle habits;
* Exposure to different environmental factors;
* Disparities in access to healthcare.
124
# **Question:**
Why are **virsuses, parasites and bacteria** risk factors of Neoplasia?
* They weaken the immune system, leaving the body more susceptible to cancer-causing infections;
* They may interfere with normal signaling pathways involved in cell growth and proliferation check points.
125
# **Examples:**
3 viruses associated with cancer
Any 3 of the following:
* Epstein-Barr Virus
* Hepatitis B Virus
* Hepatitis C Virus
* Human Immunodeficiency Virus (HIV)
* Human Papillomaviruses (HPVs)
* Human T-Cell Leukemia/Lymphoma Virus Type 1
* Kaposi Sarcoma-Associated Herpesvirus
* Merkel Cell Polyomavirus
126
# **Question:**
Why is **obesity** considered a commorbity and a risk factor of Neoplasia?
Obesity is associated with a higher risk of developing some types of cancer, since it is associated with an **increased production of insulin (in response to inflammatory processes) and estrogen (produced by fat tisssue)**, which trigger cell growth.
127
# **Question:**
Why is **type 2 Diabetes** considered a commorbity and a risk factor of Neoplasia?
Type 2 Diabetes causes insulin resistance, which means the body can't use insulin properly to keep the blood sugar at normal levels, so they become higher than normal. Insulin resistance does not mean insulin deficiency - quite the opposite, it is associated with **excess insulin**. Since insulin is known to promote cell division, excess insulin may make the organism more susceptible to develop neoplasia.
128
# **Question:**
What are the 3 classification systems of Neoplasia?
* Prognostic-based classification;
* Histogenic-based classification;
* Tumor-Nodes-Metastasis (TNM)-based classification.
129
# **Question:**
How can a neoplasia be classified according to prognostic-based classification?
* Benign;
* Malign;
* Borderline behaviour.
130
# **Question:**
Characterize malign neoplasms in terms of **cellular morphism**, **nucleus**, **mitosis** and **polarity**.
* **Cellular morphism**: pleomorphism (variable in size and shape) and anaplasia (loss of function and structure);
* **Nucleus**: big and hyperchromic (dark color), with a prominent nucleolus;
* **Mitosis**: abundant and atypical;
* **Polarity**: absent.
131
# **True or False:**
Ki-67 can be used as a proliferation marker.
**True.**
When Ki-67 is a nuclear protein that is released during cellular division. Therefore, when there is a high concentration of Ki-67, it means many cells are dividing quickly, so the cancer is more likely to grow and spread.
132
# **Complete the sentence:**
The histogenic-based classification classifies neoplasms based on the type of ____________ where they are located.
tissue
133
# **Question:**
How can a neoplasia be classified according to histogenic-based classification?
Based on the type of tissue:
* Epithelial;
* Mesenchymal or connective tissue;
* Muscle;
* Neural tissue;
* Hematologic;
* Endothelial tissue.
134
# **Question:**
What are the type of tissues associated with **carcinoma** and **sarcoma**?
Epithelial tissue and connective tissue, respectively.
135
# **Complete the sentence:**
Leukemia is a type of malign neoplasia that is located in ________ tissues.
hematological
136
# **Question:**
What is the Tumor-Nodes-Metastasis classification based on?
* Primary tumor size;
* Lymph node status (if they are swollen and/or lumpy and where they are located);
* Metastasis (by testing sentinel lymph nodes for cancer cells).
137
# **Question:**
What are the 3 phases of carcinogenesis?
1. **Initiation**: induction of DNA mutations;
2. **Promotion**: proliferation/replication of mutated cells;
3. **Progression**: acquisition of malignant properties, such as migration, invasion and metastasis.
138
# **Question:**
What is the role of cell cycle checkpoints?
They are surveillance mechanisms that monitor and control the normal cell cycle, to ensure the apropriate cell size and the replication and integrity of chromossomes.
139
# **Complete the sentence:**
At the cell cycle checkpoints, ________ are responsible of dictating the progression to the next phase of the cycle, while ________ may hold or interrupt the cell cycle progression.
| Words: cyclins, retinoblastoma protein, p53, p21
## Footnote
(NOTE: each space can have more than one word)
* first space: cyclins
* second space: retinoblastoma protein, p53, p21
140
# **True or False:**
The initiation phase of carcinogenesis begins with the lesions caused by carcinogenic agents.
**False.**
Carcinogenic agents may induce DNA mutations and damage cells, but these lesions can either be repaired or reproduced. The initiation phase of carcinogenesis begins **when the lesions can't be repaired**, not exactly when they are made.
141
# **Distinguish:**
Initiator vs. Promoter carcinogenic agent
* **Initiator** carcinogenic agent induces non-lethal mutations, causing irreversible changes to DNA;
* **Promoter** carcinogenic agent induces cell proliferation without affecting the DNA, such that its influence on cell growth is reversible.
## Footnote
(NOTE: some carcinogenic agents are both initiators and promoters)
142
# **True or False:**
Tumor supressor genes are mutations that are disadvantageous for tumor cells.
**False.**
Tumor supressor genes are mutated genes that confer advantages to tumor cells due to **loss of function**, typically as a result of frame-shift or deletion mutations.
143
# **Distinguish:**
Tumor supressor genes vs. Oncogenes
* **Tumor supressor genes** are mutated genes that confer advantages to tumor cells due to **loss of function**, typically as a result of frame-shift or deletion mutations;
* **Oncogenes** are mutated genes that confer advantages to tumor cells due to **gain of function**, typically as a result of amplification or overexpression of genes, as well as chromosomal translocations.
144
# **Question:**
In which 4 main cell mechanisms can mutated genes (tumor suppressor genes and oncogenes) interfere in?
1. Regulation of DNA repair;
2. Regulation of apoptosis (programmed cell death);
3. Growth factor signaling pathways;
4. Cell adhesion.
145
# **Question:**
Why is cell adhesion important?
* Cell-cell interaction/communication (e.g., symbiotic interactions);
* Cell-extracellular matrix interaction;
* Survival (including nutrition);
* Proliferation and differentiation;
* Tissue structure and integrity;
* Migration (including metastasis in cancer cells).
etc.
146
# **Question:**
What is the role of **cyclins** in the cell cycle?
Cyclins bind to cyclin-dependent kinases (CKD) in order to form complexes able to phosphorylate proteins from different checkpoints. Once phosphorylated, these proteins **allow the cell cycle to proceed to the next phase**.
147
# **True or False:**
Cyclin levels are overall stable throughout the cell cycle, contrarily to CKD proteins, such that the deregulation of genes involved in CKD production might affect the cell cycle progression.
## Footnote
(NOTE: CKD corresponds to cyclin-dependent kinases)
**False.**
While CKD levels are stable throughout the cell cycle, **cyclin levels vary**. Therefore, the lack of regulation (deregulation) of the genes involved in the production of cyclins might affect the progression of the cell cycle.
148
# **Question:**
What is the role of the **MYC oncogene**?
**Promotes the transcription of cyclin genes**, increasing the levels of cyclin and promoting the progression of the cell cycle. Therefore, it ultimately leads to an uncontrolled proliferation (cell growth and differentiation), while also inhibiting apoptosis.
149
# **Question:**
What are the type of genes involved in carcinogenesis?
Tumor suppressor genes and oncogenes.
150
# **Question:**
What is the role of **p53** in the cell cycle?
P53 is a transcription factor that is **activated by DNA damage, hypoxia or cell injury**. It works by activating p21, which in turn inhibits the cyclin complexes, thus stopping the cell cycle. If the damage is beyond repair, p53 can also **induce apoptosis**.
151
# **Question:**
Why is **p53 tumor suppressor** considered a tumor biomarker?
P53 tumor suppressor inhibits the activation of p53, which allows the cell cycle to progress despite DNA damage. It is considered a tumor biomarker because it is associated with multiple tumors.
152
# **True or False:**
Rb and p53 are both transcription factors that are activated by DNA damage, hypoxia and cell injury, capable of inducing apoptosis if the damage is beyond repair.
**Truth.**
153
# **Question:**
What is the role of the **Rb tumor suppressor**?
The Rb tumor suppressor inhibits the activation of Rb, allowing the cell cycle to progress despite DNA damage.
154
# **Question:**
What is the role of **retinoblastoma (Rb) protein** in the cell cycle?
Rb is a transcription factor that is activated by DNA damage, hypoxia and cell injury. It commands DNA repair mechanisms and induce apoptosis if damage is beyond repair.
155
# **Complete the sentence:**
When activated, Rb can bind with the transcription factors of the ________ family, forming complexes that inhibit the transcription of genes that allow cell cycle progression (such as cyclin).
E2F
156
# **Question:**
What are **BRCA**?
BRCA are a group of **DNA repair proteins** that resolve DNA crosslinks.
157
# **Question:**
What are the most common BRCA mutations and what type of cancers are they usually associated with?
The most common BRCA mutations, called **BRCA tumor suppressor**, are in the BRCA1 and BRCA2 genes, and they are often associated with breast and ovarian cancer.
158
# **Question:**
What is the role of the **BRCA tumor suppressor**?
BRCA tumor suppressor is related with mutations in BRCA1 or BRCA2 genes, which makes them lose their normal functions, leading to defective DNA repair and increasing the risk of accumulating mutations that evolve to cancer.
159
# **Complete the sentence:**
BCL-2 is a ________ protein, while BAX and BAK are ________ proteins.
anti-apoptotic, pro-apoptotic
160
# **True or False:**
BCL-2 is a pro-apoptotic protein.
**False.**
BCL-2 is an anti-apoptotic protein, whose overexpression due to BCL-2 oncogene may prevent apoptosis of cancer cells, allowing them to proliferate.
161
# **Question:**
What are the 2 most common **growth factor receptors** that are overexpressed or mutated in cancer?
* Epidermal growth factor receptors (EGFR);
* Epidermal growth factor receptor 2 (HER2).
162
# **Question:**
What are **growth factor receptors** (GFR)?
Growth factor receptors (GFR) are transmembrane proteins are proteins found on the surface of cells that bind to specific growth factors, which are molecules that signal the cell to proliferate (i.e., grow and divide).
163
# **Question:**
What is the **EGFR oncogene**?
The EGFR oncogene is a mutation that causes the **overexpression of the epidermal growth factor receptors (EGFR)**, allowing the survival and proliferation of cancer cells.
164
# **Question:**
What is the **Ras gene family**?
Familiy of genes that make proteins involved in cell signaling pathways/cascades that control cell growth and cell death (apoptosis).
165
# **Question:**
What is the **Ras oncogene**?
The Ras oncogene is a result of a mutation in the Ras gene family, leading to the dysregulation of major signaling cascades, thus resulting in sustained survival and proliferation of cancer cells.
166
# **Question:**
What types of cancer is **MYC oncogene** associated with?
* Burkitt lymphoma (a type of B-cell cancer);
* Small-cell lung cancer;
* Breast cancer;
* Neuroblastoma (malignant tumor in nerve cells).
167
# **Question:**
What types of cancer is **Rb tumor suppressor** associated with?
* Retinoblastoma (malignant tumor in retina);
* Small-cell lung cancer;
* Sarcoma (cancer in connective tissue).
168
# **Complete the sentence:**
MYC oncogene ________ (increases/decreases) the production of cyclins.
increases
169
# **Question:**
What types of cancer is **BCL-2 oncogene** associated with?
* Lymphomas;
* Leukemias;
* Lung cancer.
170
# **Question:**
What types of cancer is **EGFR oncogene** associated with?
* Lung cancer;
* Gliobastoma (malignant tumor in glial cells);
* Breast cancer.
etc.
171
# **Question:**
What types of cancer is **Ras oncogene** associated with?
* Pancreatic cancer;
* Lung cancer;
* Colon cancer;
* Leukemia.
172
# **Examples:**
Cell adhesion molecules
* Cadherins
* Integrins
* Selectins
173
# **Question:**
What type of cancer is **APC tumor suppressor** associated with?
Colon cancer
174
# **Question:**
What is the effect of the APC tumor suppressor gene?
The APC tumor suppressor gene has negative effects on APC proteins, making them promote migration, chromosomal instability and evasion of apoptosis, which allows cancer cells to migrate more easy and invade other tissues.
175
# **Distinguish:**
Neoadjuvant vs. Adjuvant treatment
* **Neoadjuvant treatment**: other therapies before surgery;
* **Adjuvant treatment**: surgery before other therapies.
176
# **Question:**
What are the 6 signs that a cancer cell is in its Progression phase?
1. Self-sufficient signs of growth;
2. Insensitivity to growth inhibitory signals;
3. Evasion to apoptosis;
4. Unlimited replicative potential;
5. Sustained angiogenesis;
6. Ability to invade and metastasize.
177
# **Definition:**
Angiogenesis
Formation of new blood vessels from pre-existing ones.
178
# **Question:**
What is the process that leads to tumor angiogenesis?
Tumors have a high metabolism, which means they require a lot of energy, nutrients and oxygen to support the rapid cell growth. In response to a lack of oxygen (hypoxia) and nutrients, cancer cells release angiogenic factors and promote the formation of new blood vessels surrounding the tumor - angiogenesis. Therefore, tumor angiogenesis result from the tumor's need to grow.
179
# **Question:**
What is the relation between angiogenesis and metastasis?
Angiogenesis is the formation of new blood vessels, typically as a result of a lack of oxygen and nutrients to meet the needs of a rapidly growing tumor (with a high metabolism). These new vessels are very close to the tumor cells, increasing the risk of these cells to enter the blood and migrate to other tissues, creating metastasis.
In short, angiogenesis may promote metastasis.
180
# **True or false:**
Tumor angiogenesis is promoted by chemotaxis.
**True.**
Tumor angiogenesis is promoted by nutrient and chemical concentrations (which in this case are lower that what is needed).
181
# **Complete the sentence:**
Dissemination of cancer cells can occur through ________ vessels and ________ vessels.
blood, lymphatic
182
# **Question:**
What are the 2 main factors that determine which type of vessel the cancer cells will intravasate?
* **Physical restrictions** (like proximity, fenestrations and flow mechanisms);
* **Active mechanisms for attracting cells** for specific types of vessels (like the presence of angiogenic factors).
183
# **Question:**
Describe the process of **dissemination through blood vessels**.
Tumor cells from the primary tumor:
1. Enter the blood vessels through fenestrations (**intravasation**);
2. Form an **embolus** (unattached mass that travels through the bloodstream);
3. **Adhere to vessels** membrane;
4. Escape the blood vessel through fenestrations (**extravasation**);
5. Start a **metastatic growth**.
184
# **Question:**
Is it possible to delay the process of dissemination through blood vessels? How?
Yes.
The dissemination of tumor cells through blood vessels is highly dependent on angiogenesis, which is mediated by angiogenic growth factors. So, by **counteracting** their effects using **anti-angiogenic growth factors**, it is possible to delay angiogenesis and thus the dissemination of tumor cells through blood vessels.
185
# **Question:**
Describe the process of **dissemination through lymphatic vessels**.
1. The primary tumor produces **lymphangiogenic factors**, which enter the **peritumoral lymphatic capillaries**;
2. The lymphangiogenic factors are transported up to the **sentinel lymph node** (SNL) and induce **SNL lymphangiogenesis** (formation of new lymphatic vessels) to drain the tumor;
3. These **tumor-draining vessels** have an enlarged size (with larger fenestrations, thus easier entrance) and increased lymph flow (facilitating the migration of tumor cells);
4. The lymphangiogenic factors **promote rearrangements and remodeling of smooth muscle cells** of the lymphatic vessels post-SNL;
5. The lymphangiogenic factors and metastatic cells from the lymph nodes can then pass through those vessels and reach **distal lymph nodes**;
6. There is the **promotion of secondary metastasis**.
186
# **Question:**
Each neoplasia might present different clinical manifestations, depending on which 3 factors?
* Neoplasia location;
* Neoplasia staging and degree of differentiation;
* Neoplasia ability to produce humoral factors.
187
# **Question:**
What the 3 main types of clinical manifestations of neoplasia?
* Mechanical injuries;
* Biological competition;
* Production of humoral factors.
188
# **List:**
5 types of mechanical injuries
1. Obstruction
2. Bleeding
3. Fistulation
4. Perforation
5. Compression of neighbouring structures
189
# **Question:**
What is **cachexia**?
Cachexia is a clinical manifestation of biological competition typically seen in patients in an advanced cancer stage. It consists of a complex syndrome that essentially leads to the ongoing muscle and fat loss due to increased lipolysis and proteolysis.
190
# **Question:**
Why is **anemia** a common clinical manisfestation of neoplasia?
Anemia is common in neoplasia due to:
* Hemolysis;
* Bleeding (constant loss of red blood cells and iron);
* Chronic disease;
* Chemotherapy;
* Medullar invasion (disrupting the production of red blood cells);
* Malnutrition (cancer patients usually feel sick and can't eat properly, leading to a poor intake of iron).
191
# **Distinguish:**
Signs vs. Symptoms
**Signs** can be seen by others and measured (e.g., fever), while **symptoms** are only perceived by the patient (e.g., pain).
192
# **Definition:**
Paraneoplastic syndromes
Set of signs and symptoms occuring in an oncologic situation, not directly related with the primary tumor or metastasis. They might appear in response to secondary changes in the body (e.g. in response to the elevation of a certain protein or hormone).
193
# **Definition:**
Hypercoagulability or thrombophilia
Increased tendency of blood to coagulate and form a thrombi.
194
# **True or False:**
Cancer can cause acquired hypercoagulability.
**True.**
195
# **Question:**
Why is the rate of cancer mortality increasing despite the increase in cancer research?
Due to the increase in the number of risk factors, besides the long time it takes to approve treatments (around 10 years).
196
# **True or False:**
Targeted therapy is a type of localized cancer treatment.
**False.**
Targeted therapy is a type of **systemic cancer treatment**, since it goes through the blood stream (systemically) and is able to reach the desired location.
197
# **Complete the sentence:**
Cancer treatments can be divided in ________ treatments, such as radiotherapy, and ________ treatments, such as targeted therapy.
localized, systemic
198
# **Questions:**
What are the 2 main types of localized cancer treatment?
* Sugery;
* Radiotherapy, which includes external irradiation and internal irradiation (brachytherapy).
199
# **Question:**
What are the 4 main types of systemic cancer treatment?
* Chemotherapy;
* Hormonal therapy;
* Targeted therapy;
* Immunotherapy.
200
# **True or False:**
Localized cancer treatment requires a more detailed and well defined plan, compared to systemic treatment.
**True.**
201
# **Complete the sentence:**
Blood disorders are also called ____________ disorders.
Hematological
202
# **Complete the sentence:**
Blood is constituted by 55% of ________ and 45% of ________.
plasma, formed elements
203
# **Question:**
What is plasma made of?
Plasma is the liquid part of the blood and is mostly made out of water (90%) and also contains proteins, electrolytes, carbohydrates, minerals, metabolites, etc.
204
# **Question:**
What constitutes the formed elements present in the blood?
Mostly red blood cells (nearly 100%), but also white blood cells and platelets.
205
# **Question:**
What is the **main function** of red blood cells?
Transport oxygen.
206
# **Question:**
What is the **main function** of white blood cells?
Protect the organism against external elements.
207
# **True or False:**
White blood cells can protect the organism against external and internal elements.
**True.**
Especially in the case of autoimmune diseases.
208
# **Question:**
What is the **main function** of platelets?
Participate in the coagulation process.
209
# **Complete the sentence:**
Platelets are also called ________.
Thrombocytes
210
# **Complete the sentence:**
Red blood cells are also called ________.
Erythrocytes
211
# **Question:**
Order the formed elements, from the highest volume to the lowest volume in blood.
Red blood cells > Platelets > White blood cells
212
# **Question:**
What are the 6 main functions of blood?
1. Transport oxygen
2. Transport nutrients
3. Regulate body temperature
4. Protect against foreign pathogens
5. Participate in the coagulation process
6. Regulate hydration
213
# **Definition:**
Hematopoiesis
Production of formed elements.
214
# **Question:**
Approximately, how many cells are produced daily?
Over 100 billion cells.
215
# **Question:**
Where does hematopoiesis occur?
Prenatal, first in the yolk sac, then the liver, then bone marrow.
Postnatal, mostly in bone marrow.
216
# **True or False:**
After birth, hematopoiesis occurs mainly in the bone marrow, specifically in the ribs.
**False.**
After birth, hematopoiesis occurs mainly in the bone marrow, mostly in the vertebral and pelvis.
217
# **True or False:**
All cells derive from a single hematopoietic stem cell.
**True.**
218
# **Complete the sentence:**
________ is a cytokine produced in the ________, which stimulates the production of erythrocytes.
Erythropoietin, kidneys (renal cortex)
219
# **True or False:**
Erythropoietin is a glicoprotein.
**True.**
220
# **Complete the sentence:**
________ is a cytokine produced in the ________ and the ________, which stimulates the production of thrombocytes.
Thrombopoietin, liver, kidneys
221
# **Complete the sentence:**
The differentiation of hematopoietic stem cells depends on certain elements such as ________ and ________.
cytokines, hormones
222
# **Complete the sentence:**
Erythrocytes are ________ (nucleate/anucleate), ________ (biconcave/biconvex) disk-shaped cells.
anucleate, biconcave
223
# **True or False:**
Hemoglobin is a dimer, i.e., formed by two protein subunits, alpha and beta.
**False.**
Hemoglobin is a **tetramer**, formed by 4 subunits: 2 alpha subunits and 2 beta subunits.
224
# **Complete the sentence:**
Each hemoglobin's subunit contains one ______ ______, where the oxygen will bind.
heme group
225
# **True or False:**
In hemoglobin, each heme group contains one iron atom.
**True.**
226
# **Question:**
What organ is responsible to remove erythrocytes from the circulation once they lose their function?
Spleen
227
# **True or False:**
Bilirubin is a byproduct of the breakdown of red blood cells.
**True.**
228
# **Definition:**
Hemolysis
Destruction of red blood cells.
229
# **True or False:**
Excessive hemolysis can cause jaundice.
**True.**
Hemolytic jaundice is a type of jaundice arising from excessive hemolysis (destruction of red blood cells), when the byproduct bilirubin is not excreted by the hepatic cells quickly enough, leading to its accumulation.
230
# **Complete the sentence:**
White blood cells can be classified according to the presence or absence of cytoplasmic ________.
granules
231
# **Question:**
What are the two types of non-granulocytes?
Monocytes and lymphocytes.
232
# **Complete the sentence:**
White blood cells can be divided into non-granulocytes, such as ________ and ________, or granulocytes, such as ________, ________ and ________.
| Words: neutrophils, lymphocytes, basophils, eosinophils, monocytes
monocytes, lymphocytes
neutrophils, basophils, eosinophils
233
# **Question:**
What are the functions of monocytes?
They present 3 main functions in the immune system: phagocytosis, **antigen presentation**, and cytokine production. They also participate on **tissue repair**.
234
# **Question:**
What is the main function of lymphocytes?
Recognition, specially **self** (self-antigens present on the surface of leucocytes, such as lymphocytes) **vs. non-self** (antigen structures found on the surfaces of foreign bacteria, viruses, fungi, parasites, etc.) reply
235
# **Question:**
Which is the most common type of white blood cells?
Neutrophils
236
# **Question:**
What is the main function of neutrophils?
Kill bacteria through phagocytosis.
237
# **Complete the sentence:**
White blood cells are also called ________.
Leukocytes
238
# **True or False:**
Neutrophils present a multi-lobed nuclei with large cytoplasmic granules containing highly active enzymes.
**False.**
Neutrophils present a multi-loaded nuclei with **very fine** cytoplasmic granules containing highly active enzymes.
239
# **True or False:**
Basophils normally present a uni-lobed nuclei.
**False.**
Basophils usually present a bi-lobed or tri-lobed nuclei.
240
# **Question:**
What is the main function of basophils?
Act in the case of allergies.
241
# **Complete the sentence:**
In the case of allergies, basophils secrete ________ (coagulants/anticoagulants) against hypersensitivity, such as heparin, and release histamine to ________ (contract/dilate) the blood vessels.
anticoagulants, dilate
242
# **True or False:**
Basophils and eosinophils are very similar.
**True.**
243
# **Question:**
What are the main functions of eosinophils?
Kill parasites, induce allergic reactions and release toxins to kill pathogens.
244
# **Question:**
What are megakarcyocytes?
Megakaryocyte is a large bone marrow cell with a lobated nucleus that produces blood platelets (thrombocytes).
245
# **Question:**
Besides being in the blood, in which organ are platelets mostly present?
Spleen
246
# **Distinguish:**
Homeostasis vs. Hemostasis
Hemostasis and homeostasis are two different things. Hemostasis is a biological mechanism to stop bleeding. Homeostasis is the maintenance of the body's state of balance.
247
# **Question:**
What type of cells do platelets adhere to?
Endothelial cells
248
# **Question:**
Why is it important for platelets to adhere to endothelial cells?
Endothelial cells are present in blood vessel walls, so it is important that platelets can adhere to these walls in case of rupture to help to stop the bleeding through coagulation.
249
# **True or False:**
The main function of platelets is homoestasis.
**False.**
The main function of platelets is **hemostasis**.
250
# **Question:**
Describe the shape changes that platelets undergo once activated.
First **discoid**, then **spherical** with filopodial extensions, and finally **flat**.
251
# **Question:**
What are the 4 main intervenients in hemostasis?
1. Platelets
2. Endothelial cells
3. Tissue factor-bearing cells
4. Coagulation factors
252
# **Complete the sentence:**
The intervenients of hemostasis (platelets, endothelial cells, tissue factor-bearing cells and coagulation factors) work to form a complex of cross-linked ________ and ________ to stop the bleeding.
fibrin, platelets
253
# **Complete the sentence:**
The coagulation system is well-regulated to ensure the balance between ________ factors and ________ factors.
prothrombotic (procoagulation), antithrombotic (anticoagulation)
254
# **Question:**
What suffix is added to the coagulation factors names when they're activated?
"-a"
## Footnote
E.g. Factor IIa is the activated form of Factor II.
255
# **True or False:**
The majority of coagulation factors are produced in the liver.
**True.**
256
# **Complete the sentence:**
The majority of coagulation factors are produced in the liver, yet there are exceptions such as **Factor XIII (fibrin-stabilizing factor)** which derives from ________ and **Factor VIII (antihemophilic factor)** which derives from ________.
platelets, endothelial cells
257
# **Question:**
What is the advantage of the production of coagulation factors by endothelial cells?
Endothelial cells are present in the skin and in the walls of blood vessels, which grants them **closer proximity** to possible rupture sites and ensures an **immediate and local response**.
258
# **Complete the sentence:**
Factors II, VII, IX and X depend on gammacarboxylase, a hepatic enzyme dependent
on vitamin ________.
K
259
# **True or False:**
Vitamin K helps to regulate blood coagulation by activating certain pro-coagulation factors (II, VII, IX, X).
**True.**
260
# **Question:**
What is the function of gammacarboxylase?
Converting factors II, VII, IX and X into their activated forms (i.e., IIa, VIIa, IXa and Xa).
261
# **Question:**
What does the medicine/drug Warfarin do?
Warfarin stops the recycling of vitamin K, inhibiting it's activity and, therefore, factors II, VII, IX and X don't get activated.
262
# **True or False:**
A single molecule of vitamin K can be reused many times.
**True.**
Vitamin K can be recycled.
263
# **Question:**
What are the 3 steps of hemostasis (coagulation process)?
1. **Primary Hemostasis**: vasoconstriction and platelet adhesion (creation of platelet plug).
2. **Secondary Hemostasis**: formation of fibrin, which creates a protein mesh to reinforce the plug.
3. **Fibrinolysis**: Breakdown of fibrin through plasmin (catalytic enzime), once the bleeding is controlled.
264
# **Complete the sentence:**
The secondary hemostasis involves the classical ________ ________.
coagulation cascade
265
# **Question:**
The coagulation cascade can be divided in two different ways. What are them?
The coagulation cascade can be divided into:
* Initiation, amplification and propagation
OR
* Extrinsic pathway, intrinsic pathway and common pathway
266
# **Complete the sentence:**
In the coagulation cascade, the extrinsic pathway is triggered by ________, while the intrinsic pathway is triggered by ________.
trauma to extravascular cells, internal damage to the vessel walls
267
# **Complete the sentence:**
In the common pathway of the coagulation cascade, prothrombin (factor II) is activated by converting into ________ (factor IIa), which activates fibrinogen (factor I) by converting it into ________ (factor Ia).
thrombin, fibrin
268
# **Question:**
What are the two main **coagulation analytical parameters**?
* **Prothrombin Time (PT)**: evaluates the extrinsic and common pathways of coagulation.
* **Activated Partial Thromboplastin Time (aPTT)**: evaluates the intrinsic and common pathways of coagulation.
269
# **Complete the sentence:**
To assess the effect of warfarin, we must use the ____________ (Prothrombin Time/Activated Partial Thromboplastin Time).
Prothrombin Time
270
# **Complete the sentence:**
There are two main coagulation analytical parameters: ________ is used to evaluate the intrinsic pathway, while ________ is used to evaluate the extrinsic pathway.
| Words: Prothrombin Time, Activated Partial Thromboplastin Time
Activated Partial Thromboplastin Time, Prothrombin Time
271
# **True or False:**
The coagulation pathways evaluated by the Activated Partial Thromboplastin Time and the Prothrombin Time are dependent on the tissue factor.
**False.**
* Prothrombin time (PT) evaluates extrinsic and common pathways, **depending on tissue
factor**
* Activated partial thromboplastin time (aPTT) evaluates intrinsic and common pathways, **independent of the tissue factor**.
272
# **True or False:**
Prothrombin time (PT), which evaluates extrinsic and common pathways, has normal values between 30 to 50 seconds.
**False.**
* Prothrombin time (PT) has normal values of **12-13 seconds**.
* Activated partial thromboplastin time (aPTT) has normal values of **30-50 seconds**.
273
# **Definition:**
Anemia
Anemia is an abnormally low hemoglobin (or low red blood cells) concentration.
274
# **Complete the sentence:**
A low concentration of red blood cells is called ________ and a high concentration of red blood cells is called ________.
anemia, polycythemia
275
# **Question:**
What are the possible causes of anemia?
* Hemorrhage
* Nutritional deficiencies
* Chronic diseases
(etc.)
276
# **Complete the sentence:**
Monocytes can develop into ________ or ________ cells.
macrophages, dendritic
277
# **Question:**
What is the role of the histamin and heparin released by basophils?
In case of allergies, basophils:
* release **histamin** to dilatate blood vessels and attract immune cells to the lesion.
* release **heparin** to promote the mobility of white blood cells.
278
# **True or False:**
Platelet activation occurs upon exposure to
thrombin, adenosine diphosphate or collagen.
**True.**
279
# **Question:**
What are the possible causes of polycythemia?
* Dehydration
* Adaptation to high altitude
(etc.)
280
# **Question:**
Why does the adpation to high altitudes lead to polycythemia (increased concentration of erythrocytes)?
In high altitudes there is less oxygen, causing hypoxia. To compensate for the lack of oxygen, the body tries to produce more erythrocytes in an attempt to increase the oxygen transportation to tissues. Hypoxia induces the expression of erythropoietin, which increases red blood cell production.
281
# **Complete the sentence:**
Anemia might result from differences in erythrocytes, which may be related to ________, such as microcytic, normocytic and macrocytic anemias, or related to ________, such as poikiloicytosis and anisocytosis.
size, shape
282
# **Question:**
What are the 3 types of anemia related to the size of erythrocytes?
* Microcytic (lower mean corpuscular volume)
* Normocytic (normal mean corpuscular
volume)
* Macrocytic (larger mean corpuscular
volume)
283
# **Question:**
What are the 2 most common causes of macrocytic anemia?
* Abnormal nuclear maturation of young erythrocytes
* Presence of a higher fraction of young erythrocytes
284
# **Complete the sentence:**
Megaloblastic anemias are a type of ________ anemia.
Macrocytic
285
# **Question:**
What 2 conditions is megaloblastic anemia linked to?
* Vitamin deficiencies (Vitamin B12 or folic acid)
* Hepatic disorders.
286
# **Question:**
How is megaloblastic anemia associated with alcohol comsuption?
* **Direct toxic effect** over the bone marrow, leading to ineffective erythropoiesis;
* **Folate deficiency**, since alcohol interferes with the absorption, metabolism and storage of folate, a crucial element involved in DNA synthesis. Its deficit results in impaired cell division, resulting in larger erythrocytes;
* **Liver dysfunction**, since chronic alcohol consumption can affect the normal liver function, disrupting the storage and processing of vital nutrients such as vitamin B12 (whose deficit is one of the causes of megaloblastic anemia). Moreover, the ability of liver to produce erythropoietin can also be compromised.
287
# **Complete the sentence:**
Microcytic anemia is typically linked to due to abnormalities in ________ production.
hemoglobin
288
# **Complete the sentence:**
Iron deficient anemias and Thalassemia are two types of ________ anemias.
microcytic
289
# **Question:**
What is Thalassemia?
Group of inherited conditions that affect the subunits of hemoglobin. They can be divided into alpha thalassemia (affects the alpha subunits) and beta thalassemia (affects the beta subunits).
290
# **Question:**
What are the most common causes of normocytic anemia?
* Decreased number of red cell precursors
* Low levels of erythropoietin
* Chronic inflammation (affects the availability of iron)
291
# **Complete the sentence:**
In normocytic anemia, the reduced number of red blood cells is usually linked to low levels of ________ and/or ________, which impairs the production of these cells.
erythropoietin, iron
292
# **Complete the sentence:**
Sickle cell anemia is a type of ________ (microcytic/normocytic/macrocytic) anemia. However, it can also be a result of a ________ (beta/alpha) thalassemia, which is a type of ________ (microcytic/normocytic/macrocytic) anemia.
Normocytic, beta, microcytic
293
# **Complete the sentence:**
Autoimmune hemolytic anemias are a type of normocytic anemia in which ________ cause erythrocytes destruction.
antibodies
294
# **Question:**
In sickle cell anemia, what causes the sickle shape of the erythrocytes?
In sickle cell anemia, the erythrocytes have a sickle ("foice") shape, instead of a biconcave disk shape, due to a defective hemoglobin shape.
295
# **Question:**
What are the 2 main causes of erythrocytosis?
* Increased erythropoietin production.
* Polycythemia (it’s a syndrome that leads to increased erythrocytes mass and consequently low erythropoietin).
296
# **Definition:**
Erythrocytosis
Abnormally high hemoglobin concentration.
297
# **Distinguish:**
Anemia vs. Erythrocytosis
Anemia is an abnormally low hemoglobin concentration. Erythrocytosis is an abnormally high hemoglobin concentration.
298
# **True or False:**
Anemia can be caused by an abnormally low concentration of hemoglobin or red blood cells.
**True.**
299
# **Definition:**
Polycythemia
Syndrome that leads to increased erythrocytes mass (i.e., higher concentration of red blood cells) and consequently low erythropoietin.
300
# **Complete the sentence:**
A low concentration of hemoglobin is called ________ and a high concentration of hemoglobin is called ________.
anemia, erythrocytosis
301
# **Distinguish:**
Erythrocytosis vs. Polycythemia
* Erythrocytosis: abnormally high concentration of **hemoglobin**.
* Polycythemia: abnormally high concentration of **erythrocytes**.
They are often related.
302
# **Question:**
What causes low erythropoietin in polycythemia?
An increased production of erythrocytes leads to an increased use of erythropoietin, which ultimately decreases its levels.
303
# **Complete the sentence:**
An abnormally high concentration of white blood cells is called ________ and an abnormally low concentration of white blood cells is called ________.
leukocytosis, leucopenia
304
# **Question:**
What are the possible causes of leukopenia?
* Viral infections
* Autoimmune disorders
* Side effects of medications
* Bone marrow disorders
(etc.)
305
# **Question:**
What are the possible causes of neutrophilia?
* Increased bone marrow activity (bacterial infections, acute inflammation, leukemia, etc.)
* Release from marrow pool (stress, etc.)
* Demargination into blood (stress, bacterial infections, etc.)
306
# **Question:**
What are the possible causes of leukocytosis?
* Inflammation
* Infection
* Stress response
* Trauma
* Leukemia
(etc.)
307
# **Complete the sentence:**
An abnormally high concentration of neutrophils is called ________ and an abnormally low concentration of neutrophils is called ________.
neutrophilia, neutropenia
308
# **Complete the sentence:**
An abnormally high concentration of lymphocytes is called ________ and an abnormally low concentration of lymphocytes is called ________.
lymphocytosis, lymphopenia
309
# **Questions:**
What are the possible causes of neutropenia?
* Decreased bone marrow activity (drugs, anemia, etc.)
* Decreased neutrophil survival (viral infection, sepsis, autoimmune disease, etc.)
310
# **Complete the sentence:**
Lymphoma (cancer in lymphocytes) leads to ________ (lymphopenia/lymphocytosis).
Lymphocytosis
311
# **Complete the sentence:**
An abnormally high concentration of platelets (thrombocytes) is called ________ and an abnormally low concentration of platelets is called ________.
thrombocytosis, thrombopenia
312
# **Question:**
Why do malignancies lead to thrombocytosis?
1. One of the clinical manifestations of malignancies is bleeding, which leads to an increased production of platelets in order to allow the coagulation process.
2. Some malignancies may affect the bone marrow, which consequently affects the production of formed elements and may lead to an altered (in this case, increased) production of platelets.
313
# **Definition:**
Hemophilia
Rare genetic disorder in which coagulation is affected by a **deficiency of coagulation factors**, facilititating bleeding.
314
# **Complete the sentence:**
Hemophilia A is caused by a deficiency in coagulation Factor ____, while Hemophilia B is caused by a deficiency in coagulation Factor ____.
VIII, IX
315
# **Question:**
What are the causes of **consuptive coagulopathy** or **Disseminated intravascular coagulation (DIC)** ?
* Overwhelming infections
* Massive hemorrhage
* Trauma
* Obstetric complications
* Severe burns
316
# **Question:**
What happens in **consuptive coagulopathy** or **Disseminated intravascular coagulation (DIC)**, that makes it very hard to treat?
1) Widespread activation of the clotting system ⭢ 2) Excessive formation of blood microclots:
* Blockage in small vessels and organ dysfunction
* ⬇ **coagulation factors and platelets** ⭢ Bleeding tendencies ⭢ 1)
## Footnote
(It is a non-ending cycle)
317
# **Question:**
What are the 2 main **possible causes** of iron deficiency anemia?
* Deficient intake of iron (or malabsorption of iron)
* Blood loss
318
# **Question:**
What are the general **clinical manifestations** of iron deficiency anemia?
* Tiredness
* Weakness
* Shortness of breath
* Pale skin and mucosa
* Tachycardia
* Fragile skin appendages (brekage in nails and hair)
319
# **Question:**
Why is **pale skin** a clinical manifestation of iron deficiency anemia?
Pale skin is caused by the decreased number of **red** blood cells in the blood.
320
# **Question:**
Can iron deficiency anemia have **gastrointestinal clinical manifestations**?
Yes.
* Glossitis (swollen and inflamed tongue)
* Achlorhydria (absence of stomach acid)
* Hematochezia (red, fresh blood in feces)
* Melena (black, old blood in feces)
321
# **Question:**
What is **Pica**?
Pica is a rare clinical manifestation of iron deficiency anemia, where people crave non-alimentary products such as clay or dirt.
322
# **Question:**
Where is iron primarily absorbed in the body?
Duodenum
323
# **Complete the sentence:**
In an anemic scenario, the body will attempt to ________ (increase/decrease) the iron uptake.
increase
324
# **Question:**
Why does the body increase the iron uptake in an **hypoxia** scenario?
Hypoxia corresponds to the lack of oxygen. Tissues and organs require oxygen (and nutrients) to survive, so the body will attempt to increase the supply of oxygen to the tissues by increasing the number of oxygen transporters, aka red blood cells. Red blood cells contain iron, so an increase in the production of red blood cells requires an increase in iron levels, which is achieved by an increased iron uptake.
325
# **Complete the sentence:**
Lower levels of iron will ________ (increase/decrease) the levels of hepcidin.
Decrease
326
# **Question:**
What is the role of hepcidin in the recycling of iron?
Hepcidin controls the passage from iron accumulation places to plasma (blood). Therefore, hepcidin plays a crucial role in processes that allow the body to store iron, relocate it and reuse it.
327
# **Complete the sentence:**
Hepcidin binds to ________, leading to its lysossomal degradation.
Ferroportin
328
# **Definition:**
Ferroportin
Ferroportin is a transmembrane protein that transports iron from the inside of a cell to the outside of the cell - it is an iron exporter.
329
# **Definition:**
Hepcidin
Hormone/protein that regulates iron uptake, namely
330
# **Complete the sentence:**
High levels of hepcidin makes it ________ (easier/harder) for ferroportin to transport iron to your bloodstream, ________ (enabling/preventing) iron absorption.
harder, preventing
331
# **True or False:**
Ferroportin is responsible for storing the iron, transports it from the bloodstream to the liver.
**False.**
Ferroportin transports iron from the duodenum into the bloodstream, allowing it to be reused instead of stored.
332
# **Truth or false:**
Hepcidin binds to ferroportin to allow the release of iron into the bloodstream.
**False.**
Hepcidin binds to ferroportin to stop it from releasing the iron into the bloodstream. In other words, hepcidin binds to ferroportin to store the iron in the liver.
333
# **Complete the sentence:**
In case of iron deficiency anemia, the levels of hepcidin are ________ (high/low).
low
334
The blood always flows from _______ (higher/lower) pressure regions to _______ (higher/lower) pressure regions.
higher, lower
335
How is the mean arterial pressure calculated?
Mean Arterial Pressure = Cardiac Output x Peripheral Vascular Resistance
336
Changes in blood pressure are detected by _________ and corrected by _________.
the carotid and aortic sinus baroreceptors, the baroreflex and RAA system
337
Which hormones are responsible for controlling the peripheral vascular resistance?
Atrial Natriuretic Peptide (ANP), Vasopressin, Epinephrin, Angiotensin II
338
True or False: Both the sympathetic and parasympathetic nervous systems control the peripheral vascular resistance.
True
339
The cardiac function is measured by the ________.
cardiac output
340
What are the determinants of cardiac function?
Heart rate and stroke volume
341
How is cardiac output calculated?
Cardiac Output (mL/min) = Heart Rate (/min) x Stroke Volume (mL)
342
What are the determinants of the heart rate?
Electrical conduction system,sympathetic nervous system, and parasympathetic nervous system.
343
What are the 5 main determinants of stroke volume?
Volemia, end diastolic volume, blood pressure, ventricular wall thickness, and contractility.
344
What is the stroke volume?
Volume of blood pumped by the left ventricle during each systolic contraction.
345
What is the baroreflex?
Homeostatic mechanism that helps to regulate blood pressure.
346
The baroreflex is more sensitive to ___________ (increase/decrease) in blood pressure.
Decrease
347
Where are the most sensitive baroreceptors located?
Carotid sinuses and aortic arch.
348
What are baroreceptors?
Strech receptors (or mechanoreceptors) that sense blood pressure.
349
What happens when the baroreflex detects a decresase in blood pressure?
Increase in heart rate + Increase in contractility of the left ventricle + Increase in peripheral vascular resistance
350
What does RAAS stand for?
Renin-Angiotensin-Aldosterone System
351
The aortic arch baroreceptors are predominantly responsive to ___________ (increases/decreases) in blood pressure.
Increases
352
True or False: A decrease in blood pressure leads to the stretching of baroreceptors, triggering a depolarizing receptor potential.
**False.** An increase...
353
A decrease of blood pressure leads to a decreased stretch of baroreceptors, triggering a __________ (depolarizing/hyperpolarizing) potential.
hyperpolarizing
354
The baroreflex is a ________ (fast/slow) response to changes in blood pressure.
Fast
355
The RAA system is a ________ (fast/slow) response to changes in blood pressure.
Slow
356
Why is the baroreflex faster than the RAA system in responding to changes in blood pressure?
Because the baroreflex is a **neural response**, which is faster than the **hormonal response** of RAA.
357
The RAA system regulates blood pressure by regulating ____________.
blood volume
358
Renin converts ___________ to _____________.
Angiotensinogen, angiotensin I
359
Angiotensin II causes the _____________ (vasodilation/vasoconstriction) of the arterioles, leading to ___________ (increased/decreased) peripheral vascular resistance.
vasoconstriction, increased
360
What is the first step of the RAA system?
Release of the enzyme Renin in the kidney in response to reduced perfusion pressure.
361
What enzyme is responsible for converting Angiotensin I to Angiotensin II? Where does this conversion happen?
Angiotensin Converting Enzyme (ACE). It happens mainly in the lung endothelium, but also happens in smaller quantities in the renal endothelium.
362
Angiotensin II ________ (increases/decreases) H2O and Na+ reabsorption.
Increases
363
What are the main 10 risk factors of cardiac disease?
1. Sex
2. Age
3. Familial hereditary traits
4. Tobacco use
5. Hypertension
6. Diabetes mellitus
7. Dyslipidemia (abnormal levels of lipids in the blood)
8. Obesity (IMC > 30kg/m2)
9. Stress
10. Inadequate lifestyles (sedentarism, sodium and hypercaloric-based diet, drug abuse)
364
What is a heart failure?
Decrease or loss of the heart's pumping ability.
365
What are the 7 general main causes of heart failure?
1. Ischemic heart disease
2. Hypertension
3. Medication
4. Arrhythmias
5. Cardiomyopathy
6. Pericardial disease
7. Endocardial disease
366
Can a chronic heart failure turn into an acute heart failure?
Yes, due to **decompensation** as a result of new medication or new disease.
367
What is the ejection fraction and how is it calculated?
The ejection fraction is the portion of blood present in the left ventricle at the end of the diastolic filling that is pumped by the left ventricle in the systolic contraction. It is calculated as:
EF (%) = Amount of blood **pumped out** / Amount of blood **in the chamber**
368
In systolic dysfunction, the ejection fraction is _________ (increased/normal/reduced).
Reduced
369
In diastolic dysfunction, the ejection fraction is ___________ (elevated/normal/reduced).
Normal
370
What are the 6 main general causes of systolic dysfunction?
1. Ischemic heart disease
2. Endocardial disease
3. Hypertension
4. Diabetes mellitus
5. Renal disease
6. Infiltrative disease
371
What are the main 3 specific causes of systolic dysfunction?
1. Arrythmias
2. Myocarditis
3. Dilated cardiomyopathy
372
What are the 3 main specific causes of diastolic dysfunction?
1. Pericardial disease
2. Hypertrophic cardiomyopathy
3. Restritive cardiomyopathy
373
What are two conditions that can lead to left heart failure due to volume overload?
Anemia and hyperthyroidism
374
What is one cause of left heart failure due to volume overload?
Valvular insufficiency
375
Name two causes of left heart failure related to pressure overload.
Hypertension and ejection obstruction
376
What is AV valvular stenosis, and how does it contribute to left heart failure?
It is the narrowing of the atrioventricular valve, reducing the filling of the left ventricle and leading to heart failure.
377
Besides AV valvular stenosis, name two other causes of left heart failure due to decreased filling.
Pericardial disease and infiltrative diseases
378
How does myocardial infarction lead to left heart failure?
It causes the loss of cardiomyocytes, reducing the heart’s ability to pump effectively.
379
What connective tissue diseases can contribute to left heart failure?
Diseases that cause fibrosis or inflammation of the myocardium, leading to loss of heart function.
380
How do infections contribute to decreased heart contractility and left heart failure?
They can cause myocarditis, leading to inflammation and weakening of the heart muscle.
381
What are the two main causes of decrease in heart contractility and, consequently, left heart failure?
Toxic substances (drugs, alcohol, etc.) and infections
382
What is systolic dysfunction in left heart failure?
A condition where end-diastolic volume (EDV) is greater than stroke volume (SV), leading to decreased cardiac output.
383
What are the 3 compensatory mechanisms that the heart uses to maintain cardiac output in systolic dysfunction?
* Frank-Starling mechanism
* Increase in catecholamines (↑HR, ↑SV)
* Myocardial hypertrophy (↑EDV ⇒ ↑SV)
| EDV - end-diastolic volume; SV - stroke volume
384
What happens when compensatory mechanisms in systolic dysfunction fail?
Heart failure persists, leading to reduced cardiac output and systemic complications.
385
What is diastolic dysfunction in left heart failure?
A condition where end-diastolic pressure increases due to impaired ventricular relaxation.
386
In diastolic dysfunction, there is a ____________ (decreased/increased) relaxation capability, ____________ (decreased/increased) elastic tension and ____________ (decreased/increased) ventricular rigidity.
Decreased, decreased, increased
387
Is contractility affected in diastolic dysfunction?
No, contractility is generally kept!
388
Left heart failure leads to ____________ (increased/decreased) cardiac output and ____________ (increased/decreased) blood pressure.
decreased, decreased
389
Why is there an increased Sympathetic Nervous System (SNS) activity after heart failure?
It's a compensatory mechanism in which the body tries to increase heart rate and contractility to compensate for low cardiac output.
390
How does heart failure affect cardiac output and blood pressure?
It decreases cardiac output (↓CO) and decreases blood pressure (↓BP).
391
What is the role of the sympathetic nervous system (SNS) in left heart failure?
The sympathetic NS is activated to compensate for reduced cardiac output, leading to vasoconstriction and increased afterload.
392
How does left heart failure affect the renal system?
It increases renin-angiotensin-aldosterone (RAA) system activation and increases vasopressin, which contribute to fluid retention and vasoconstriction.
393
What inflammatory mediators are increased in heart failure?
Cytokines such as interleukins (ILs) and tumor necrosis factor-alpha (TNFα), as well as endothelins.
394
How does heart failure contribute to structural heart changes?
It leads to cardiomyocyte hypertrophy (enlargement of heart muscle cells) and increased vasoconstriction.
395
What hemodynamic effects are seen in left heart failure?
Increased afterload and increased blood pressure due to compensatory mechanisms.
396
The activation of the sympathetic nervous system in heart failure leads to ________________, which is the narrowing of veins, and to ________________, which is the narrowing of arteries.
venoconstriction, vasoconstriction
397
Venoconstriction increases ____________ (preload/afterload) and vasoconstriction increases ____________ (preload/afterload).
preload, afterload
398
What is preload and afterload?
Preload is the initial stretching of the cardiac myocytes (muscle cells) prior to contraction. It is related to ventricular filling. In other words, preload is the amount of blood filling the heart
Afterload is the force or load against which the heart has to contract to eject the blood. In other words, afterload is the resistance the heart has to pump against.
399
In left heart failure, the kidneys sense a ________ (high/low) blood pressure and activate the RAA system.
low
400
What are the two main neuro-endocrine systems activated in response to low blood pressure in heart failure?
Sympathetic Nervous System (SNS) and Renin-Angiotensin-Aldosterone System (RAAS)
401
What are the effects of increased Sympathetic Nervous System (SNS) activity in heart failure?
Venoconstriction (increased preload) and Vasoconstriction (increased afterload)
402
What are the effects of the Renin-Angiotensin-Aldosterone System (RAAS) activation in heart failure?
Increased Glomerular Filtration Rate (GFR) and Increased Vasopressin (ADH), which both lead to fluid retention.
403
What is the result of the compensatory mechanisms in early heart failure on preload and afterload?
Increased preload and Increased afterload
404
What inflammatory mediators are increased in chronic heart failure?
Cytokines (ILs, TNFα) and Endothelins
405
What is the result of persistent neuro-endocrine activation on blood pressure in chronic heart failure?
Increased blood pressure
406
True or False: Left heart failure triggers neuro-endocrine responses to maintain blood pressure and cardiac output.
True
407
True or False: The neuro-endocrine responses to left heart failure lead to decreased preload and afterload, worsening heart failure.
False.
The neuro-endrocrine responses **increase preload and afterload**, worsening heart failure.
408
In left heart failure, ____________ (increased/decreased) resistance in the systemic circulation leads to left ventricular insufficiency, which causes congestion in the pulmonary circulation.
increased
409
In left heart failure, there is ________ (resistance/congestion) in the systemic circulation and ________ (resistance/congestion) in the pulmonary circulation.
resistance, congestion
410
True or False: Left ventricular insufficiency leads to congestion in pulmonary circulation.
True.
Left ventricular insufficiency is the inability of the left ventricle to pump blood effectively, which leads to congestion, i.e. buildup of blood, in the pulmonary circulation.
411
What are the 7 main clinical manifestations of left heart failure?
* Dyspnea (shortness of breath)
* Nocturnal paraoxystic dyspnea (sensation of shortness of breath that awakens the patient)
* Ortopnea (difficulty breathing when lying down)
* Cardiac asthma (a type of coughing or wheezing that occurs with left heart failure)
* Fatigue and mental confusion
* Nocturia (the need for patients to get up at night regularly to urinate)
* Thoracic pain
412
True or False: Cardiogenic pulmonary edema is one of the main complications of left heart failure.
True.
Cardiogenic pulmonary edema is mainly caused by left ventricular failure and it is a life-threatening collection of too much fluid in the lungs.
413
Can left heart failure lead to right heart failure?
Yes, in fact it is one of the main causes.
414
What is Cor Pulmonale?
Cor Pulmonale is an enlarged right ventricle of the heart, caused by a primary disorder of the respiratory system, and it may cause right heart failure.
415
What are the 3 primary causes of Cor Pulmonale?
* **Hypoxia-induced vasoconstriction:** pulmonary vascular resistance rapidly increases as oxygen tension decreases.
* **Pulmonary embolism:** it's a blood clot that develops in a blood vessel elsewhere in the body (often the leg), travels to an artery in the lung, and suddenly forms a blockage of the artery.
* **COPD (Chronic Obstructive Pulmonary Disease):** happens when the lungs become inflamed, damaged and narrowed.
416
What congenital conditions can cause Pre-capillary Obstruction?
Congenital shunts or obstructions.
417
What cardiac event can lead to Cardiomyocyte Loss (loss of heart muscle cells in the right ventricle) in the right ventricle?
Acute myocardial infarction (right ventricle)
418
What are the four main categories of causes for right Heart Failure?
* Left Heart Failure
* Cor Pulmonale
* Pre-capillary Obstruction
* Cardiomyocyte Loss
419
What is a cause of Pre-capillary Obstruction characterized by high blood pressure in the pulmonary arteries?
Idiopathic pulmonary hypertension
420
In right heart failure, ____________ (increased/decreased) resistance in the pulmonary circulation leads to right ventricular insufficiency, which causes congestion in the systemic circulation.
increased
421
In left heart failure, there is a ________ congestion, while in right heart failure there is a ________ congestion.
pulmonary, systemic
422
Pulmonary disease (e.g. Cor Pulmonale) is a common cause of ________ (left/right) heart failure.
right
423
In left heart failure, there is a ________ (aortic/pulmonary) valve stenosis, while in right heart failure there is a ________ (aortic/pulmonary) valve stenosis.
aortic, pulmonary
424
What are the main clinical manifestations of right heart failure?
* Systemic venous congestion
* Dyspnea
425
What is a visible sign of systemic venous congestion in the neck?
Jugular venous distention (or jugular venous turgescence)
426
What occurs in the splanchnic territory due to hepatic congestion in Right Heart Failure?
Hepatojugular reflux, ascites, abdominal pain
427
What is the term for generalized severe edema involving multiple venous territories?
Anasarca
428
What previous condition can cause dyspnea in Right Heart Failure?
Previous Left Heart Failure (leading to pulmonary edema)
429
What is ischemic heart disease?
Heart damage caused by narrowed heart arteries, which result in poor blood and oxygen supply to the heart.
430
What is the most frequent cause of ischemic heart disease?
Atherosclerosis (buildup of fats, cholesterol and other substances in and on the artery walls).
431
What are some factors that can trigger vasospasm in coronary arteries?
Histamine, serotonin, catecholamines, endothelial factors, and medications.
432
Does vasospasm-induced ischemic heart disease have a relation to exertion?
No
433
What is a potential source of emboli that can cause ischemic heart disease?
Endocarditis vegetations (growths on heart valves).
434
What is the primary congenital cause of ischemic heart disease?
Coronary abnormalities.
435
What are the 4 main general causes of ischemic heart disease?
1. **Atherosclerosis** (buildup of fats, cholesterol and other substances in and on the artery walls).
2. **Vasospasm** (a condition in which an arterial spasm leads to vasoconstriction).
3. **Embolism** (an obstruction or blockage in a blood vessel).
4. **Congenital ischemic heart disease** (birth defects that affect the normal way the heart works).
436
True or False: Atherosclerosis, as a cause of ischemic heart disease, is not related to exertion.
False.
Atherosclerosis is often related to exertion (physical activity).
437
Ischemia occurs with ____ % occlusion while resting and ____ % occlusion during exertion.
90, 50
438
Ischemia pathophysiology can originate due to ________ (increased/decreased) O2 consumption and/or ________ (increased/decreased) O2 delivery.
increased, decreased
439
What are the 3 main causes of an increased O2 consumption, that might lead to ischemia?
* **Thyrotoxicosis**: occurs when there are abnormally high blood levels of the thyroid hormones, triiodothyronine (T3) and thyroxine (T4), which increase metabolic rate (i.e., increase the heart's oxygen demand).
* **Aortic stenosis**: narrowing of the aortic valve opening, which causes an increased workload that leads to left ventricular hypertrophy (thickening of the heart muscle) and this enlarged muscle requires more oxygen.
* **Medication**
440
What are the 3 main causes of an decreased O2 delivery, that might lead to ischemia?
* **Coronary obstruction**: a thrombus (blood clot) can obstruct or completely block an artery, leading to severe ischemia or infarction.
* **Carbon Monoxide (CO) poisoning**: CO binds to hemoglobin in red blood cells much more strongly than oxygen. This reduces the oxygen-carrying capacity of the blood, leading to tissue hypoxia (oxygen deficiency).
* **Medication**
441
How can rupture of plaque lead to ischemia?
**Plaque rupture** happens when the fibrous cap that covers the plaque breaks open. With plaque erosion, the fibrous cap stays intact, but endothelial cells around the plaque get worn away, causing **endothelial dysfunction**. Both events lead to the formation of a blood clot, due to **platelet aggregation**, and to the **release of autacoids** (local hormones produced in tissues), such as thromboxane A2 and serotonin. All of this leads to a **decrease in perfusion** (aka ischemia).
442
What are the autacoids (local hormones) released after plaque rupture, during platelet aggregation?
**Thromboxane A2** (potent platelet activator and vasoconstrictor, produced by activated platelets during hemostasis) and** serotonin** (released by platelets to narrow arterioles, slowing blood flow and helping to form clots).
443
Rupture of plaque leads to a ____________ (decrease/increase) in perfusion, resulting in ischemia.
decrease
444
What happens to PO2 levels due to decreased perfusion?
Decreased perfusion leads to a decrease in the partial pressure of oxygen (PO2) in cells.
445
What metabolic process occurs in cells due to decreased PO2?
The lack of oxygen leads to anaerobiosis (lactic acid production) and glycogen depletion.
446
What is the direct result of the changes in cellular metabolism due to decreased perfusion?
Cellular lesion
447
What is the clinical manifestation of cellular lesion in ischemic heart disease?
Angina pectoris (chest pain)
448
What are the 4 main changes in cellular metabolism due to reduced perfusion in ischemia?
1. Decrease in PO2
2. Anaerobiosis (lactic acid) and glycogen depletion
3. Mitochondrial “edema” and membrane lesion (cellular lesion)
4. Dysfuncion of contraction-relaxation cycle
449
True or False: Angina pectoris is an early manifestation of ischemia.
False.
Angina pectoris is considered a "late" manifestation of angina (after 30s).
450
True or False: Angina pectoris aggravates with respiration.
False.
Angina pectoris does not aggravate with respiration.
451
What is the evolution of angina pectoris?
First, it is a stable angina (pain only in exertion). Then it becomes unstable (pain while resting as well). And finally it presents as an acute myocardial infarctation, where the pain is uninterrupted for over 10 minutes.
452
True or False: Most patients with myocardial infarctation are assymptomatic.
True.
Myocardial infarctation is assymptomatic in 80% of patients.
453
Why are most myocardial infarctation patients assymptomatic?
1. Transient perfusion decrease (that resolves).
2. Afferent nervous dysfunction (for example, due to cardiac transplantation or diabetes mellitus, which make them feel less pain).
3. Different thresholds of pain.
454
What are the main 4 clinical manifestations of angina pectoris?
1. S4 and dispnea: systolic and diastolic dysfunction.
2. Nausea and voming: activation of the vagus nerve.
3. Tachycardia (fast heart rate): increased catecholamine levels.
4. Bradycardia (slow heart rate): lesion of the AV node (infarction by occlusion of the right coronary artery) and activation of the vagus nerve.
## Footnote
NOTE: Catecholamines increase heart rate, blood pressure, breathing rate.
455
What gastrointestinal symptoms can occur in angina pectoris or myocardial infarction?
Nausea and vomiting
456
What nerve activation is associated with nausea and vomiting in angina pectoris/myocardial infarction?
Activation of the vagus nerve
457
What cardiac manifestation can occur due to a lesion of the AV node in myocardial infarction?
Bradycardia (slow heart rate)
458
What are the main complications of acute myocardial infarctation?
* Cardiogenic shock (hypotension due to severe HF)
* Arrhythmias
* Thrombosis
459
What happens when acute myocardial infarction causes occlusion of the descending left coronary artery?
There is a rupture of the ventricular septum, allowing **interventricular communication**.
460
What complication happens when acute myocardial infarction causes occlusion of the left anterior descending coronary artery and the circumflex artery?
Cardiac tamponade
461
Arrythmias may cause ventricular fibrillation, which ________ (lowers/increases) cardiac output and leads to acute myocardiac infarctation.
lowers
462
Why is thrombosis a complication of acute myocardial infarctation?
Because there is activation of the factors of hemostasis by the damaged myocardium, which lead to venous stasis and thrombosis.
463
What are the 4 valves of the heart?
* Aortic
* Pulmonary
* Mitral
* Tricuspid
464
What are the two main categories of valve disease?
* Valve stenosis (valves can't open properly)
* Valve insufficiency (valves can't close properly)
465
Order the following steps:
* Pulmonary hypertension
* Aortic stenosis
* Obstruction of ejection in the left ventricle
* Systolic dysfunction
* Left ventricular hypertrophy
* Left heart failure
* Right heart failure
1. **Aortic stenosis** (narrowing of the aortic valve, which connects the LV to the aorta)
2. **Obstruction of ejection in the LV** (the narrowed valve will restrict the blood flow out of the LV to the aorta)
3. **Left ventricular hypertrophy** (compensatory response to the increased pressure in the LV, where there is a thickening and enlargement of heart muscle in the LV walls).
4. **Systolic dysfunction** (the heart becomes inable to meet its demand and generate sufficient arterial blood pressure and cardiac output)
5. **Left heart failure** (the left ventricle is gradually weakened and loses its ability to pump blood to the systemic circulation)
6. **Pulmonary hypertension** (abnormally high blood pressure in the pulmonary circulation, due to narrowing of the arteries, which demands an even higher pressure in the right ventricle to be able to pump the blood to the pulmonary arterie)
7. **Right heart failure** (the right ventricle is unable to pump enough blood to the pulmonary circulation)
466
What is aortic stenosis?
Narrowing of the aortic valve opening (between the left ventricle and the aorta) that restricts blood flow from the left ventricle to the aorta.
467
What is aortic insufficiency?
Regurgitation (backflow) of the blood from the aorta into the left ventricle, when the aortic valve can't close properly.
468
What are the compensatory mechanisms for acute regurgitation?
None
469
What are the compensatory mechanisms for chronic regurgitation (e.g. in aortic insufficiency)?
Long QT interval
## Footnote
The QT interval is the time from the beginning of the QRS complex, representing ventricular depolarization, to the end of the T wave, resulting from ventricular repolarization.
470
What are the 3 main manifestations of left heart failure due to aortic insufficiency?
* Dyspnea (cardiogenic pulmonary oedema)
* Arterial hypotension
* Hyperdynamic pulses
471
True or False: A prolonged QT interval is a marker of advanced aortic insufficiency.
True.
A long QT interval is a compensatory mechanism of chronic aortic insufficiency.
472
What is mitral stenosis?
Narrowing or blockage of the mitral valve, which is located between the left atrium and the left ventricle.
473
What are 4 main types of mitral stenosis?
* **Rheumatic mitral stenosis** (narrowing og the mitral valve as a consequence of rheumatic fever, an autoimmune inflammatory process that causes inflammation in many organs, including the heart)
* **Dystrophic calcification** (which causes mitral stenosis): dystrophic calcium deposition to the mitral valve.
* **Congenital heart malformation** (abnormal morphology of the mitral valve)
* **Tumoral mitral stenosis** (narrowing of the mitral valve due to a tumor)
474
Order the following steps:
* Pulmonary hypertension
* Dilation of the left atrium
* Mitral stenosis
* Right heart failure
* Obstruction of the filling of the left ventricle
1. **Mitral stenosis** (narrowing of the mitral valve, restricting the blood flow from the left atrium to the left ventricle)
2. **Obstruction of the filling of the left ventricle**
3. **Dilation of the left atrium** (enlargement of the left atrium due to pressure or volume overload)
4. **Pulmonary hypertension** (the dilation of the left atrium compressses the pulmonary artery, causing an increased blood pressure)
5. **Right heart failure** (the right ventricle is not able to pump blood to the pulmonary circulationdue to the high blood pressure in the pulmonary artery)
475
Mitral stenosis leads to ____________ (increased/decreased) ventricular diastolic filling, ____________ (increased/decreased) cardiac output and ____________ (increased/decreased) distal perfusion (i.e. organ and tissue perfusion).
**decreased** (the blood cannot pass from the left atrium to the left ventricle)
**decreased** (since there is less blood in the left ventricle, less blood is pumped out of the heart)
**decreased** (less blood pumped out of the heart means less blood reaching organs and tissues)
476
What are the 3 main clinical manifestations of mitral stenosis?
* Pulmonary edema (dyspnea, ortopnea, nocturnal paraoxystic dyspnea)
* Fatigue
* Palpitations (arrhythmia)
477
What are the 3 main cardiomyopathies?
* Dilated cardiomyopathy
* Hypertrophic cardiomyopathy
* Restrictive cardiomyopathy
478
What are cardiomyopathies?
Diseases of the myocardium (heart muscle).
479
What are the 6 clinical manifestations of dilated cardiomyopathy?
* Dyspnea (shortness of breath) during exertion
* Angina pectoris (chest pain)
* Palpitations
* Abdominal and peripheral edema (inflammation)
* Jugular venous turgor (visually enlarged jugular vein)
* Bilateral pulmonary rales or crackles (abnormal lung sounds heard during auscultation, described as crackling or bubbling sounds)
480
What are the 3 clinical manifestations of hypertrophic cardiomyopathy?
* Dyspena
* Dizziness
* Fainting
481
What are the 4 clinical manifestations of restrictive cardiomyopathy?
* Dyspnea
* Right heart failure symptoms
* Kussmaul sign (an increase in the jugular venous pulse when the patient inhales)
* Fourth heart sound (S4) (an abnormal heart sound)
482
What is the Frank-Starling mechanism?
The Frank-Starling mechanism is a physiological principle that explains how the heart responds to changes in venous return. Increases in venous return cause the heart's chambers to fill with more blood, which then causes the heart to stretch and contract more forcefully, and pump more blood out to the rest of the body.
483
What is the principle of Starling's law?
It states that the force of ventricular contraction is increased when the ventricle is stretched prior to contraction.
484
Order the following steps in dilated cardiomyopathy:
* Systolic dysfunction
* Frank-Starling mechanism
* Eccenctric hypertrophy and left ventrical dilation
* Cardiotoxic factors
1. Cardiotoxic factors (factors that damage the heart's muscle or lead to eletrophysiology dysfunction)
2. Frank-Starling mechanism
3. Eccentric hypertrophy and left ventrical dilation
4. Systolic dysfunction
485
Cardiac lesion leads to ____________ (increased/decreased) contractility, triggering the Frank-Starling mechanism.
decreased
486
In dilated cardiomyopathy, the increased ventricular diastolic filling (VDF) leads to ____________ and ____________.
1. **Eccentric hypertrophy** (characterized by increasing myocyte length, which ultimately results in a dilated left ventricle with thin walls)
2. **Left ventricle dilation**
487
Dilated cardiomyopathy is caracterized by ____________ (increased/decreased) contractility.
decreased
488
What is dilated cardiomyopathy?
It's a type of myocardium (heart muscle) disease that causes the heart chambers (ventricles) to thin and stretch, growing larger and becoming unable to pump blood by losing its contractility.
489
What is hypertrophic cardiomyopathy?
It's a type of myocardium (heart muscle) disease that causes the thickening of the heart muscle, compromising the ventricular diastolic filling due to lower ventricular volume.
490
In dilated cardiomyopathy, the walls of the ventricles become ________ (thinner/thicker) due to an ____________ (eccentric/concentric) hypertrophy.
thinner, eccentric
491
In hypertrophic cardiomyopathy, the walls of the ventricles become ________ (thinner/thicker) due to an ____________ (eccentric/concentric) hypertrophy.
thicker, concentric
492
Order the following steps in hypertrophic cardiomyopathy:
* Mitral insufficiency
* Concentric hypertrophy
* Cardiotoxic factors
* Hypertrophy of the interventricular septum
1. Cardiotoxic factors (factors that damage the heart's muscle or lead to eletrophysiology dysfunction)
2. Hypertrophy of the Interventricular septum (wall that separates the two ventricles)
3. Concentric hypertrophy (abnormal increase in left ventricular myocardial mass caused by chronically increased workload on the heart)
4. Mitral insufficiency
493
True or False: In hypertrophic cardiomyopathy, the left ventricle wall becomes thicker than the interventricular septum.
**False.**
The hypertrophy in the interventricular septum is larger than the hypertrophy of the left ventricle. Harmful factors damage the heart, causing the wall between the ventricles to thicken more than the left ventricle's main wall.
494
Hypertrophic cardiomyopathy is caracterized by ____________ (increased/decreased) obstruction to ejection.
increased
495
In hypertrophic cardiomyopathy, an increased obstruction to ejection leads to ________ (concentric/eccentric) hypertrophy, which ________ (increases/decreases) the volume of the left ventricle, further increasing obstruction to ejection.
* **concentric** (thickening of the left ventricle walls)
* **decreases** (the walls become thicker, resulting in less chamber volume)
496
What is restrictive cardiomyopathy?
It's a myocardium disease in which the muscle tissue in the ventricles becomes stiff, restricting the filling of the ventricles and leading to reduced blood flow in the heart.
497
What causes the increased stiffness of the myocardium in restrictive cardiomyopathy?
Connective tissue proliferation
498
What is compliance?
The term compliance is used to describe how easily a chamber of the heart or the lumen of a blood vessel expands when it is filled with a volume of blood. Physically, compliance (C) is defined as the change in volume (ΔV) divided by the change in pressure (ΔP).
499
In restrictive cardiomyopathy, elasticity is ________ (increased/decreased) and compliance is ________ (increased/decreased).
decreased (the muscle tissue becomes stiff), decreased (the muscle tisse can't expand properly)
500
What happens to the atriums in restrictive cardiomyopathy?
The atriums become dilated due to loss of elasticity and compliance.
501
What is the main consequence of restrictive cardiomyopathy?
Systemic venous congestion
502
In restrictive cardiomyopathy, the volume of the ventricles ____________ (increases/decreases) and the volume of the atriums ____________ (increases/decreases).
decreases, increases
503
True or False: In restrictive cardiomyopathy, the ventricles walls become thicker, which reduces the volume of the ventricles.
True
504
In hypertrophic cardiomyopathy, why does concentric hypertrophy lead to mitral insufficiency?
The narrowing caused by hypertrophy and increased velocity of blood flow through the obstructed area can lead to mitral regurgitation (blood leaking back through the mitral valve) **due to the Venturi effect** (a decrease in pressure in areas of high flow velocity).
505
What is the Venturi effect?
The Venturi effect describes how the velocity of a fluid increases as the cross section of the container it flows in decreases.
506
True or False: In restrictive cardiomyopathy, the ejection fraction is normal or decreased.
False.
In restrictive cardiomyopathy, the ejection fraction is normal or **increased**.
507
What is pericardial disease?
It's an **inflammatory** process involving the pericardium, a fibrous, double-walled and fluid-filled sac that surrounds the heart and great vessels.
508
An acute pericardial disease is called ________, which can evolve to chronical pericardial disease called ____________.
Pericarditis, Pericardial effusion
## Footnote
Pericardial effusion = derrame pericárdico
509
What are the main 4 causes of pericardial disease?
* Infection
* Trauma
* Acute myocardial infarctation
* Connective tissue disorder
510
What is Pericarditis?
Pericarditis is an inflammation of the pericardium.
511
What is Pericardial effusion?
A pericardial effusion is an abnormal accumulation of fluid in the pericardial cavity.
512
In pericarditis, calcium deposition occurs in the ________ (acute/chronic) inflammatory phase, while fibrin deposition occurs in the ________ (acute/chronic) inflammatory phase.
chronic, acute
513
Why is the heart filling compromised by chronic pericarditis (pericardial effusion)?
The accumulation of fluid in the pericardial cavity constricts the heart due to buildup of pressure, compromising the heart's ability to fill up with blood.
514
True or False: In chronic pericarditis, there is fibrous cicatrization of the pericardium.
True
515
What are 3 main clinical manifestations of (acute) pericarditis?
* Intermittent fever
* Pleuritic pain (sharp chest pain that worsens during breathing)
* Pericardial friction rub sound in auscultation (resembles the sound of squeaky leather)
516
What are the hepatic clinical manifestations of pericardial effusion?
Hepatomegaly and hepatojugular reflux (hepatic venous congestion)
517
What is the main consequence of pericardial effusion?
The heart filling is compromised, reducing cardiac output and leading to pulmonary and systemic circulation congestion due to regurgitation.
518
What are the 5 main manifestations of systemic and pulmonary congestion in pericardial effusion?
1. Dyspnea
2. Fatigue
3. Kussmaul's sign
4. Hepatomegaly
5. Hepatojugular reflex
519
What are the pulmonary clinical manifestations of pericardial effusion?
Dyspnea and fatigue (pulmonary edema)
520
What is the Kussmaul's sign?
It's an increased jugular venous pressure with inspiration, which leads to a visible jugular venous distention.
521
Besides the manifestations of systemic and pulmonary congestion, what are the other two main manifestations of pericardial effusion?
* **Paradoxical Pulse** (abnormal decrease in pulse wave amplitude during inspiration)
* **Pericardial Knock** (a high-pitched sound made by the heart due to early diastole, as a ventricle does not fully fill with blood between heartbeats)
522
What is arrhythmia?
Abnormal or irregular heartbeat
523
Distinguish the two main types of arthythmia.
* **Bradyarrhythmia** (Sinus bradycardia): slower-than-typical heart rate (< 60 bpm).
* **Tachyarrhythmia** (Sinus tachycardia): faster-than-typical heart rate (> 100 bpm).
524
What is the sick sinus syndrome?
## Footnote
Sick sinus syndrome = Síndrome do nódulo sinusal
Alternating bradycardia and tachycardia
525
What is an atrioventricular block?
It's a heart rhythm disorder that causes alterations in the atrioventricular electrical conduction, which becomes slower or blocked.
526
How many degrees of block are there in atrioventricular block?
Three
527
What is fibrillation?
Rapid, erratic heartbeats (uncoordinated series of very rapid, ineffective contractions of the ventricles) that cause the heart to abruptly stop pumping blood.
528
Is age a risk factor of atrial fibrillation?
Yes, it is more common in old age
529
What causes atrial fibrillation?
Irregular electrical activity with multiple sites of auricular depolarisation.
530
In atrial fibrillation, the P-wave is ________ (normal/prolonged/shortened/absent) and the QRS complexes are ________ (normal/irregular/absent).
absent, irregular
531
Why is there a risk of thromboembolism in atrial fibrillation?
The irregular electrical activity in the heart leads to inneficient auricular contraction, which causes blood to stagnate within the atriums and stagant blood is more prone to clotting, increasing the risk of forming a thrombi.
532
What causes ventricular fibrillation?
Irregular electrical activity with multiple sites of ventricular depolarisation.
533
In ventricular fibrillation, the P-wave is ________ (normal/prolonged/shortened/absent) and the QRS complexes are ________ (normal/irregular/absent).
absent, absent
534
What is more serious: atrial or ventricular fibrillation? Why?
Ventricular fibrillation, as it may lead to cardiac arrest and death.
535
What is shock?
Rapid decrease in arterial blood pressure, with reduced blood flow to the organs, leading to their dysfunction.
536
What are the 3 main types of shock?
1. Hypovolemic Shock
2. Distributive Shock
3. Cardiogenic Shock
537
Hypovolemic Shock is caused by a decrease in ________.
blood volume (volemia)
538
Distributive Shock is caused by a decrease in ________.
vascular resistance
539
Cardiogenic Shock is caused by a decrease in ________.
cardiac output
540
What causes the decreased vascular resistance in Distributive Shock?
Systemic vasodilation and capillary drainage
541
What are the consequences of Cardiogenic Shock?
It's characterized by **low blood pressure** (systolic below 90 mmHg), **decreased cardiac output**, and **reduced urine output (oliguria)**, indicating that the kidneys are not receiving enough blood flow.
542
What are the 3 main causes of Distributive Shock?
Distributive shock occurs when there's widespread vasodilation (widening of blood vessels) and/or capillary leak, leading to a relative decrease in blood volume. This can be caused by:
* **Septic shock**: Due to severe infection.
* **Neurogenic shock**: Due to damage to the nervous system.
* **Anaphylactic shock**: Due to a severe allergic reaction.
543
Connect each uppercase letter with the respetive lowercase letter:
A. Cardiogenic shock
B. Hypovolemic shock
C. Distributive shock
a. Volume-related
b. Blood vessel-related
c. Heart-related
A. c
B. a
C. b
544
In shock, a ________ (high/low) blood pressure leads to ________ (high/low) levels of oxygen in the blood, causing organ damage.
low, low
545
What are the 3 main complications of shock?
* **Acute Renal Failure/Acute Kidney Injury**
* **Disseminated Intravascular Coagulation (DIC)**: abnormal blood clotting throughout the body's blood vessels.
* **Acute Respiratory Distress Syndrome (ARDS)**: lung failure due to fluid buildup in your lungs and low blood oxygen levels.
546
In shock, metabolism and body temperature are ________ (increased/decreased).
decreased
| (due to low oxygen)
547
What are the risks of untreated Pericarditis?
* Pericardial effusion → Cardiac tamponade (life-threatening compression of the heart).
* Recurrent pericarditis (especially in autoimmune causes).
* Constrictive pericarditis (fibrosis leading to heart failure).
548
# **Complete the sentence:**
The vascular system is also known as ________________ system.
circulatory
549
# **Question:**
What does the vascular system include?
Blood vessels and Lymph vessels
550
# **Question:**
Distinguish the blood from the lymph in terms of constitution.
The blood is made of **55% plasma** (which is 90% water and 10% proteins, electrolytes, carbohydrates, minerals, etc.) and **45% formed elements** (almost 100% red blood cells and around 2% of platelets and white blood cells).
The lymph is made of **96% water** and **4% solid parts** (which mainly include immune cells, but also proteins, amino acids, lipidic elements, etc.).
551
# **Question:**
What is the main function of blood?
Deliver oxygen and nutrients to the organs and recover metabolic residues.
552
# **Question:**
What is the main function of lymph?
Transport immune cells and drain interstitial fluids accumulated in excess in tissues.
553
# **True or False:**
The lymph and the blood circulate in a closed loop system, with a central pump.
**False.**
The blood circulates in a closed system, with the heart as a central pump, but lymph circulates in an open system without a main pump.
554
# **Question:**
Distinguish blood and lymph in terms of color.
Blood is a reddish fluid, while lymph is a clear colorless or yellowish fluid.
555
# **Question:**
What are the two main types of blood vessels?
Venous vessels and Arterial vessels
556
# **Choose the correct option:**
Regarding blood volume distribution:
a) The blood volume is equally distributed between venous and arterial vessels.
b) The majority of blood volume is within arterial vessels.
c) The majority of blood volume is within venous vessels.
c)
| Venous vessels have 64% of blood, while arterial vessels have ~15%.
557
# **Question:**
Distinguish venous and arterial vessels in terms of function.
Venous vessels transport deoxygenated blood, while arterial vessels transport oxygenated blood.
558
# **True or False:**
Venous vessels and arterial vessels are equally distributed in the body.
**True.**
559
# **Question:**
Name the three types of arterial vessels.
* Arteries
* Arterioles
* Capillaries
560
# **Question:**
Name the three types of venous vessels.
* Veins
* Venules
* Capillaries
561
# **Question:**
What are the four layers of blood vessels?
1. **Lumen:** interior of the vessels, where the blood flows.
2. **Tunica intima**: inner layer of endothelial cells.
3. **Tunica media**: intermediate layer of smooth muscle.
4. **Tunica adventitia/externa**: outer layer of connective tissue.
562
# **Match each number with the respective letter:**
1) Tunica intima
2) Tunica media
3) Tunica adventitia/externa
a) Connective tissue
b) Endothelial cells
c) Smooth muscle
1) b
2) c
3) a
563
# **Question:**
Distinguish arterial vessels and venous vessels in terms of **lumen diameter** and **wall thickness**.
Arterial vessels have a smaller lumen (shorter diameter) than venous vessels.
Arterial vessels have thicker walls than venous vessels.
564
# **Complete the setence:**
In ____________ (arterial/venous), typically the tunica adventitia is thicker than the tunica media.
venous
565
# **True or False:**
Both arterial and venous vessels present vasa vasorum and nervi vasorum in tunica adventitia.
**True.**
566
# **Question:**
Distinguish the tunica intima of arterial and venous vessels.
Tunica intima of arterial vessels is **rough** or **wavy**, while in venous vessels it is **smooth**.
567
# **Question:**
What are vasa vasorum and nervi vasorum?
**Vasa vasorum** are small blood vessels that self-irrigate blood vessels.
**Nervi vasorum** are nerves present in blood vessels that control their contraction and dilation.
568
# **Question:**
What is the thicker layer of arterial vessels?
Tunica media
569
# **Question:**
Why do venous vessels present valver?
To prevent blood regurgitation.
570
# **Complete the sentence:**
Larger arterial vessels present ________ (less/more) elasticity.
more
571
# **Question:**
Distinguish larger arterial and venous vessels in terms of elasticity.
**Arterial vessels are more elastic than venous vessels.** Therefore, tunica intima and tunica media of arterial vessels present elastic membranes, and these are absent in venous vessels.
572
# **Question:**
What do larger arterial vessels present in tunica intima and tunica media?
Larger arterial vessels present an internal elastic membrane in tunica intima and an external elastic membrane in tunica media.
573
# **Complete the sentence:**
Veins are considered ____________ vessels, for retaining a great portion of blood volume.
capacitance
574
# **Question:**
What is the main function of capillaries?
Supplying blood to tissues by perfusion.
575
# **Question:**
What distinguishes different types of capillaries?
Size and type of fenestrations.
576
# **Question:**
What is the wall of capillaries made of?
Capillaries wall is constituted by an endothelial layer surrounded by a basement membrane (thin, pliable sheet-like type of extracellular matrix).
577
# **Question:**
What are the three types of capillaries?
1. Continuous capillaries
2. Fenestrated capillaries
3. Sinusoidal capillaries
578
# **Question:**
What type of fenestrations do continuous capillaries present?
They have a complete endothelial lining with **tight junctions** between endothelial cells, which are only permeable to small molecules.
579
# **Question:**
What type of fenestrations do fenestrated capillaries present?
They present **pores/fenestrations** in the endothelial lining, besides the tight junctions, making them permeable to larger molecules.
580
# **Question:**
What type of fenestrations do sinusoidal capillaries present?
They have extensive intracellular gaps and incomplete basement membranes, in addition to intercellullar clefts and fenestrations.
581
# **Question:**
What are is the most common type of capillaries? And the least common?
The most common type of capillaries is continuous capillaries and the least common type is sinusoidal capillaries.
582
# **Question:**
Where are fenestrated capillaries found in the body?
Kidneys and small intestine
583
# **Question:**
Where are sinusoidal capillaries found in the body?
Liver, spleen, bone marrow and lymph nodes.
584
# **Question:**
What is the particularity of sinusoidal capillaries, since they have more fenestrations?
Blood flow is very low, allowing for more time for exchanges of substances.
585
# **Question:**
Why do capillaries allow substances exchange?
Because they present fenestrations and are leaky.
586
# **Question:**
Lymphatic vessels are interlaced among blood capillaries, except in...
Central nervous system, bone marow, bones, teeth and cornea.
587
# **Question:**
What are lymphatic vessels made of?
Lymphatic vessels present an endothelial linen in the inner part and present three coats, similarly to blood vessels (including contractile walls of smooth muscle).
588
# **Question:**
Do lymphatic vessels have valves?
Yes, they have semilunar valves to prevent backflow of lymph.
589
# **Question:**
What is the importance of controlling interstitial fluid levels?
To maintain the normal blood and lymph volumes.
590
# **Complete the sentence:**
The interstitial fluid enters ____________ vessels through loose junctions. Then, it drains to ____________ vessels and, in case of excess of fluid, it drains to the right and left ____________________.
capillary lymphatic, lymphatic, subclavian veins
591
# **Complete the sentence:**
Vessels conducting the fluid to a lymph node are called ________ vessels, whereas vessels conducting the fluid away from the lymph nodes are called ________ vessels.
afferent, efferent
592
# **Question:**
Describe a laminar flow.
A laminar flow is the typical blood flow, where there is a growing flow as there is a proximity to the center of the vessel (such that the blood nearest to the walls does not move). This type of flow is smooth and almost silent.
593
# **Question:**
When is blood flow turbulent?
Blood flow may become turbulent due to:
* Contraction of the heart valves, which accelerate the flow.
* Obstruction of blood vessels.
594
# **Complete the sentence:**
Turbulent blood flow emits a turbulent noise, which can be a ________ (murmur/bruit) when heard over blood vessels or a ________ (murmur/bruit) when heard over the heart.
bruit, murmur
## Footnote
Bruit is the sound heard in arterial obstruction.
595
# **Complete the sentence:**
The flow of the blood between the two ends of the circulatory system depend on the ________ difference generated by the heart (as the pump) and on the ____________ to the flow offered by the blood vessels.
pressure, resistance
596
# **Question:**
How does the viscosity of blood affect the velocity of blood flow?
Higher viscosity, lower velocity.
597
# **Question:**
How does the radius of the vessel affect velocity, resistance and pressure?
⬇ radius
⬇ velocity of blood flow
⬆ resistance
⬆ pressure
598
# **Complete the sentence:**
Arterial pressure is typically measured around the upper arm at the heart level with a ________. It relies on an auscultatory methods based on the sounds of ________.
sphygmomanometer, Korotkoff
599
# **Question:**
What controls the resistance of the vessels?
Hormones (e.g., vasopressin, angiotensin II, epinephrin) and neural system.
600
# **Complete the sentence:**
Arterial pressure is detected by ________________ and controlled by ________________ and ________________.
baroreceptors, baroreflex, reninangiotensin-aldosterone (RAA) system
601
# **Question:**
Write the mathematical formula of mean arterial pressure.
Mean arterial pressure = cardiac output x resistance of the vessels
602
# **Complete the sentence:**
Cardiac output is affected by ________ and ____________.
heart rate, stroke volume
603
# **Question:**
Why do men have higher blood pressure?
Estrogen reduces arterial pressure and men have less estrogen than women.
604
# **Complete the sentence:**
The higher the blood pressure, the ________ (lower/higher) the risk.
higher
## Footnote
Risk of hypertension and hypertensive crisis.
605
# **Complete the sentence:**
Cardiovascular adjustments are achieved by changes in the ____________________ and in ________________________.
cardiac output, blood vessels diameter
606
# **Question:**
What are the five main actions to control blood vessels diameter?
1. Action of vasodilator metabolites
2. Autoregulation
3. Action of vasoregulatory substances produced by endothelial cells
4. Action of circulating vasoactive hormones
5. Action of vasomotor nerves
607
# **Question:**
What is the role of vasodilator metabolites?
Active tissues produce metabolic byproducts that influence blood vessel dilation to increase blood supply.
608
# **Question:**
How do vasodilator metabolites work in the case of hypercarnia (high levels of CO₂)?
**Pathway of Vasodilation:**
1. **Increased CO₂ (Hypercapnia)** → More CO₂ leads to an increase in H⁺ (protons).
2. **Increased H⁺** → Lowers pH (acidifies the environment).
3. **Activation of K⁺ channels** → Allows potassium to flow out of endothelial cells.
4. **Hyperpolarization of endothelial cells** → Reduces intracellular calcium (Ca²⁺).
5. **Reduced intracellular calcium** → Leads to **vascular relaxation and vasodilation**.
609
# **Question:**
What are the main vasodilator metabolites?
CO₂ (carbon dioxide) and K⁺ (potassium)
610
# **Question:**
How does increased CO₂ lead to vasodilation?
Increased CO₂ increases H⁺ levels, lowering pH, which activates K⁺ channels (K⁺ leaves the cells), leading to hyperpolarization of endothelial cells and reduced intracellular calcium, causing vasodilation.
611
# **Question:**
What is the role of K⁺ in vasodilation?
Sodium-potassium channels open, allowing K⁺ to leave the cell and causing hyperpolarization of endothelial cells, which reduces intracellular calcium and leads to vascular relaxation and dilation.
612
# **Question:**
Why does lowering intracellular calcium cause vasodilation?
Calcium is essential for muscle contraction; reducing calcium relaxes the vascular smooth muscle, leading to dilation.
613
# **Question:**
What happens when endothelial cells become hyperpolarized?
It reduces intracellular calcium, which results in vascular relaxation and increased blood flow.
614
# **Question:**
What is autoregulation in the cardiovascular system?
The ability of tissues to maintain a relatively constant blood flow during changes in perfusion pressure.
615
# **Question:**
What is the importance of vasodilation in case of hypercapnia?
Hypercapnia corresponds to increased CO₂ levels. The goal is to remove CO₂ and increase O₂ levels. Therefore, vasodilation will help to increase gases exchange.
616
# **Question:**
What triggers the autoregulation response in blood vessels?
An increase in pressure inside the vessels.
617
# **Question:**
How do smooth muscles in blood vessels respond to increased pressure?
Increased pressure inside the vessels causes smooth muscle stretching, leading to smooth muscle contraction to regulate blood flow.
618
# **Question:**
What is the main function of smooth muscle contraction in autoregulation?
To counteract excessive blood flow by reducing vessel diameter, maintaining stable tissue perfusion.
619
# **Question:**
Why is autoregulation important for organs like the brain and kidneys?
These organs require a stable blood supply to function properly, regardless of fluctuations in blood pressure.
620
# **Question:**
What are the two main substances secreted by the endothelium that regulate blood vessel function?
**Prostacyclin** (promotes vasodilation) and **Thromboxane A₂** (promotes clot formation and vasoconstriction).
621
# **Question:**
What is the precursor molecule for both prostacyclin and thromboxane A₂?
Arachidonic acid.
622
# **Question:**
Which enzyme is involved in converting arachidonic acid into prostacyclin and thromboxane A₂?
Cyclooxygenase (COX).
623
# **Question:**
Where is prostacyclin primarily produced, and what is its main function?
Produced by endothelial cells, it promotes vasodilation and inhibits platelet aggregation.
624
# **Question:**
Where is thromboxane A₂ primarily produced, and what is its main function?
Produced by platelets, it promotes clot formation (platelet aggregation) and vasoconstriction.
625
# **Question:**
Why is a balance between prostacyclin and thromboxane A₂ important?
To ensure clots form when necessary (e.g., injury) while preventing excessive clotting that could block blood flow.
626
# **Complete the sentence:**
Prostacyclin is produced by ________________ (platelets/endothelial cells) and promotes ________________ (vasodilation/vasoconstriction).
endothelial cells, vasodilation
627
# **Complete the sentence:**
Thromboxane A₂ is produced by ________________ (platelets/endothelial cells) and promotes ________________ (vasodilation/vasoconstriction).
platelets, vasoconstriction
628
# **Question:**
How does aspirin affect the production of prostacyclin and thromboxane A₂?
Aspirin **irreversibly inhibits cyclooxygenase (COX)**, reducing the production of both prostacyclin (vasodilation, anti-clot) and thromboxane A₂ (vasoconstriction, pro-clot).
629
# **Question:**
Why does aspirin have a stronger effect on thromboxane A₂ than prostacyclin?
Platelets lack a nucleus and cannot synthesize new COX enzymes, so thromboxane A₂ production remains inhibited for the lifespan of the platelet (**days**). In contrast, endothelial cells can regenerate COX within **hours**, allowing prostacyclin levels to recover faster.
630
# **Question:**
Why is aspirin commonly used as a blood thinner and to reduce formation of thrombus?
By inhibiting thromboxane A₂, aspirin reduces platelet aggregation and clot formation.
631
# **Question:**
What enzyme catalyzes the production of nitric oxide (NO) from arginine?
Endothelial nitric oxide synthase (NOS3)
632
# **Question:**
What is the function of nitric oxide (NO) in the cardiovascular system?
NO is a vasodilator that relaxes vascular smooth muscle, reducing blood pressure and increasing blood flow.
633
# **Question:**
How is nitric oxide (NO) produced in endothelial cells?
NO is synthesized from arginine by nitric oxide synthase (NOS3), activated by intracellular Ca²⁺.
634
# **Question:**
What is the role of cyclic guanosine monophosphate (cGMP) in vasodilation?
NO activates soluble guanylyl cyclase, increasing cGMP, which promotes vascular smooth muscle relaxation.
635
# **Question:**
What happens if NO production is reduced?
Reduced NO leads to less vasodilation, causing higher blood pressure and increased vascular resistance.
636
# **Question:**
Why does administering certain arginine analogs increase blood pressure?
Some analogs of arginine inhibit NOS activity, reducing NO production and leading to vasoconstriction and increased blood pressure.
637
# **Question:**
What intracellular ion activates NOS3 in endothelial cells?
Calcium (Ca²⁺)
638
# **Question:**
How does NO induce vasodilation?
| NO = Nitric Oxide
NO diffuses into smooth muscle cells → Activates soluble guanylyl cyclase → Increases cyclic GMP (cGMP) → Relaxes vascular smooth muscle → Vasodilation
639
# **Question:**
What happens to blood pressure when NO production is increased?
Blood pressure decreases due to vasodilation.
640
# **Complete the sentence:**
When activated, the cGMP cascade leads to ____________ (vasoconstriction/vasodilation).
vasodilation
641
# **Question:**
What are endothelins, and where are they found?
Endothelins are polypeptides found in several cells, including vascular endothelial cells and smooth muscle cells.
642
# **Question:**
How many types of endothelins are there, and which two are found in vascular endothelial and smooth muscle cells?
There are three types of endothelins (ET-1, ET-2, ET-3), but ET-1 (the most abundant) and ET-3 are found in vascular endothelial and smooth muscle cells.
643
# **Question:**
Distinguish endothelin A (ETA) and endothelin B (ETB) receptors in terms of affinity to endothelins.
* ETA receptor has a **great affinity for ET-1**.
* ETB receptor has **equal affinity for all** endothelins (ET-1, ET-3).
644
# **Question:**
Where are endothelin receptors located in the cardiovascular system?
* **Vascular smooth muscle cells** (have both ETA and ETB receptors).
* **Vascular endothelial cells** (have only ETB receptors).
645
# **Question:**
What happens when endothelin receptors on vascular smooth muscle cells are activated?
When endothelin receptors on vascular smooth muscle cells are activated, they lead to **vasoconstriction**.
646
# **Question:**
What type of endothelin receptors are in vascular smooth muscle?
Endothelin A (affinity for ET-1) and Endothelin B (affinity for ET-1 and ET-3) receptors.
647
# **Question:**
What type of endothelin receptors are in vascular endothelial cells?
Only endothelin B receptors (equal affinity for ET-1 and ET-3).
648
# **Question:**
What happens when endothelin B receptors on endothelial cells are activated?
When endothelin B receptors on endothelial cells are activated, they lead to the production of nitric oxide (NO) via nitric oxide synthase (NOS), which activates the cGMP cascade and leads to NO-dependent smooth muscle relaxation and, finally, **vasodilation**.
649
# **Question:**
Why do endothelin receptor activation lead to vasoconstriction in smooth muscle cells and vasodilation in endothelial cells?
Although ETB receptors are present on both cell types, their effects are quite different:
* In smooth muscle, activation of ETA and ETB receptors leads to vasoconstriction due to the increase in intracellular calcium.
* In endothelial cells, activation of ETB receptors leads to the production of NO, which causes vasodilation in the surrounding smooth muscle cells.
650
# **Question:**
Name four vasoconstrictor circulatory hormones.
* Norepinephrine
* Epinephrine
* Vasopressin
* Angiotensin II
651
# **Question:**
Name five vasodilation circulatory hormones.
* Vasoactive intestinal peptide (VIP)
* Kinins
* Atrial natriuretic peptide (ANP)
* Brain natriuretic peptide (BNP)
* C-type natriuretic peptide (CNP)
652
# **Question:**
What are natriuretic peptides, and what role do they play in the cardiovascular system?
Natriuretic peptides (ANP, BNP, CNP) regulate blood pressure, fluid balance, and vascular tone by promoting diuresis and vasodilation.
653
# **Question:**
Which receptors do natriuretic peptides bind to, and what is the outcome of this binding?
Natriuretic peptides bind to NPR-A and NPR-B receptors, which are guanylyl cyclase enzymes that catalyze the conversion of GTP into cyclic GMP (cGMP).
654
# **Question:**
What is the function of cGMP in the body?
cGMP is a second messenger that causes vasodilation, promotes diuresis and natriuresis (increased sodium and water excretion in the kidneys, respectively), and reduces aldosterone secretion.
655
# **Question:**
What is the effect of natriuretic peptides on vascular smooth muscle?
Natriuretic peptides trigger the production of cGMP, which increases the **relaxation** of smooth muscle and leads to vasodilation.
656
# **Complete the sentence:**
Natriuretic peptides (ANP, BNP, CNP) activate the ________ cascade, leading to ____________ (vasodilation/vasoconstriction).
cGMP, vasodilation
657
# **Question:**
What is the role of baroreceptors in regulating blood pressure?
Baroreceptors detect changes in blood pressure. When blood pressure decreases, they initiate neural responses to restore blood pressure to normal levels.
658
# **Question:**
What happens when baroreceptors detect a decrease in blood pressure?
When baroreceptors detect a **decrease** in blood pressure, they stimulate the release of **vasopressin** (also known as antidiuretic hormone, ADH).
659
# **Question:**
How does vasopressin help restore blood pressure after a decrease?
Vasopressin is a vasoconstrictor hormone that **increases contractility of the heart** and promotes **vasoconstriction**, both of which help to increase blood pressure.
Vasopressin also **increases water reabsorption** in the kidneys and **decreases NaCl excretion**, which helps to increase blood volume and raise blood pressure.
660
# **Question:**
What is the overall effect of baroreceptor activation when blood pressure is low?
Baroreceptor activation leads to vasopressin release, which increases water reabsorption, decreases NaCl excretion, increases heart contractility, and induces vasoconstriction, all contributing to an increase in blood pressure.
661
# **Question:**
What are varicose veins?
Twisted, bulging and enlarged veins.
662
# **Question:**
Where do varicose veins most often occur and why?
Legs, due to increased pressure (from blood accumulation) in the veins of the lower body from standing and walking.
663
# **Question:**
List six common causes of varicose veins.
1. Genetic susceptibility
2. Long periods of standing
3. Long periods of sitting
4. Pregnancy
5. Age
6. Obesity
664
# **Question:**
List common symptoms of varicose veins.
* Pain, heaviness or discomfort
* Leg cramps and swelling of the legs
* Itching and sores around the ankles or legs
* Burning sensation
* Changes in the skin, like change in skin color (blue-ish tone) or thickening of the skin
665
# **Question:**
What are the main 2 imaging techniques used to diagnose varicose veins?
Ultrasound and Venogram (X-ray test that shows blood flow in veins)
666
# **Question:**
What are the three main treatment options for varicose veins?
1. Lifestyle changes
2. Compression (socks)
3. Surgery
667
# **Question:**
What lifestyle changes and habits can a patient adopt to effectively manage and alleviate the symptoms of varicose veins?
* Avoid prolonged standing or sitting
* Lose weight
* Exercise to improve circulation
* Use compression socks
668
# **Question:**
What is vasculitis?
Inflammation of the blood vessels.
669
# **Question:**
What are the main complications of vasculitis?
Vasculitis can impair organ perfusion, which can cause ischemia (reduced blood flow), necrosis (tissue death), and inflammation of various organs, depending on the affected blood vessels.
670
# **Question:**
What are the potential causes of vasculitis?
Vasculitis can be a primary disorder or secondary to other causes, and it can be either autoimmune or non-autoimmune.
671
# **Question:**
What clinical manifestations can vasculitis present?
Vasculitis can present with systemic symptoms (affecting the whole body) or organ-specific symptoms (affecting particular organs).
672
# **Question:**
What is the initial cause of the thickening and stiffening of arterial walls in atherosclerosis?
The thickening and stiffening of arterial walls in atherosclerosis is caused by the accumulation of lipids, fibrous elements, and calcifications.
673
# **Question:**
How do alterations in the endothelium contribute to atherosclerosis?
Alterations in the endothelium allow the infiltration of low-density lipoproteins (LDL) into the subendothelial region, which is a key step in atherosclerosis.
674
# **Question:**
What happens to LDL after it infiltrates the subendothelial region in atherosclerosis?
LDL can be oxidized, and the oxidized LDL is recognized by scavenger receptors on macrophages, triggering a cascade of events.
675
# **Question:**
What is the role of macrophages in the development of atherosclerosis?
Oxidized LDL induces the recruitment of monocytes, which differentiate into macrophages, **leading to the formation of foam cells. These foam cells contribute to fatty streaks and plaque formation**.
676
# **Question:**
What is the effect of cholesterol accumulation in macrophages during atherosclerosis?
**Cholesterol accumulation in macrophages can be lipotoxic**, damaging the endoplasmic reticulum and triggering macrophage apoptosis and plaque necrosis.
677
# **Question:**
How does cholesterol accumulation contribute to atherosclerotic plaque formation?
Cholesterol accumulation promotes the formation of cholesterol crystals, which contribute to the development of atherosclerotic plaques.
678
# **Question:**
What is the role of the fibrous cap in stabilizing an atherosclerotic plaque?
The fibrous cap forms over the necrotic core of the plaque, helping to stabilize the plaque and prevent rupture.
679
# **Question:**
Regarding atherosclerosis, what happens to macrophages within the plaque over time?
Accumulated macrophages continue to die and remain retained within the plaque, leading to an increase in the necrotic core.
680
# **Question:**
How does plaque calcification occur in atherosclerosis?
The death of macrophages and vascular smooth muscle cells leads to the calcification of the plaque.
681
# **Question:**
What are the possible outcomes of an atherosclerotic plaque?
An atherosclerotic plaque can cause vessel occlusion or, more commonly, plaque rupture, which triggers thrombosis and blocks blood flow.
682
# **Question:**
What does oxidized LDH do?
Oxidized LDH will stimulate the release of
proinflammatory cytokines that will activate
macrophages and stimulate vascular smooth
muscle cells to produce collagen.
683
# **Question:**
Name some of the risk factors of Atherosclerosis.
* Male gender (low estrogen)
* Family history of ischemic heart disease or stroke
* Hypertension
* Diabetes Mellitus type 1 and 2
* Hyperlipedemia (e.g. high colesterol)
* Obesity
* Smoking (carbon monoxide induces ischemia which enhances formation of plaques)
(etc.)
684
# **Question:**
What are the two main clinical manifestations of atherosclerosis **at the heart**?
Angina pectori (myocardium accumulate “pain-producing” substances) and myocardial infarction (complete occlusion or clotting of coronary arteries).
685
# **Question:**
What is the main clinical manifestation of atherosclerosis **at the brain**?
If there is a complete occlusion or clotting of a brain artery it can lead to **thrombotic strokes.**
686
# **Question:**
What are the two main clinical manifestations of atherosclerosis **at the abdominal aorta**?
Typically, extensive atherosclerotic plaques can led to **aneurismal dilatation** and subsequent **aortic rupture**.
687
# **Question:**
What is the main clinical manifestation of atherosclerosis **at the legs**?
Renal vessels constriction can
cause **renovascular hypertension**.
688
# **Question:**
What is the main clinical manifestation of atherosclerosis **at the legs**?
Atherosclerotic plaques can result in **intermittent claudication**, i.e., fatigue and pain that worsen on walking and are relieved at rest.
689
# **Complete the sentence:**
Hypertension is called ________________ hypertension, if it has multiple known causes, or ____________ hypertension if the cause is unknown.
secondary, essential
## Footnote
Essential hypertension can also be called idiopathic or primary hypertension.
690
# **Question:**
What are the four main factors associated with hypertension?
Hypertension is mostly associated with:
1. **Increased peripheral vascular resistance** (due to vasoconstriction or endothelial dysfunction).
2. **Increased cardiac output** (higher heart rate or stroke volume).
3. **Increased blood volume** (due to excess sodium and water retention).
4. **Increased blood viscosity** (which increases resistance to blood flow).
691
# **Question:**
What are the clinical manifestations?
Hypertension mostly presents nonspecific symptoms such as headaches, fatigue and dizziness.
Nevertheless, when not treated it can result in other complications, such as heart failure, myocardial ischemia and infarction, aneurysms, retinopathy, hemorrhagic stroke, renal failure, etc.
692
# **Question:**
How can hypertension lead to heart failure?
Hypertension corresponds to high arterial pressure. This leads to increased afterload, which is the pressure that the heart must work against to eject blood during systole (ventricular contraction), therefore leading to systolic dysfunction. Additionally, in order to be able to support such high arterial pressure, the left ventricle (LV) wall thickness, leading to LV hypertrophy, which ultimately will impair ventricle relaxation during filling, resulting in diastolic dysfunction. The combination of both diastolic and systolic dysfunction will induce heart failure. Heart failure occurs when the heart muscle doesn't pump blood as well as it should.
693
# **Question:**
How can hypertension lead to myocardial ischemia and infarction?
Myocardial infarction, colloquially known as "heart attack," is caused by decreased or complete cessation of blood flow to a portion of the myocardium. Hypertension (high arterial blood pressure) may lead to arterial damage, which accelarates atherosclerosis, specially in coronary vessels (that irrigate the myocardium), leading to decreased myocardial blood and oxygen supply and, therefore, myocardial ischemia and infarction.
694
# **Question:**
What are the risk factors of hypertension?
* Gender
* Obesity
* Lack of Physical Activities
* Age
* Genetic
* Stress and Anxiety
* Sodium consumption
* Alcohol consumption
* Smoking
* Caffeine
695
# **Question:**
What is circulatory shock?
Condition associated to an inadequate tissue perfusion in consequence of inadequate cardiac output or inadequate volemia inside blood vessels.
696
# **Question:**
What are the four main types of circulatory shock?
1. Hypovolemic shock
2. Distributive or vasogenic shock
3. Cardiogenic shock
4. Obstructive shock
697
# **Question:**
What is hypovolemic shock?
Inadequate tissue perfusion due to **reduced blood volume**.
698
# **Question:**
In which scenarios can hypovolemic shock occur?
Can occur in scenarios of hemorrhage, trauma, surgery, burns or severe fluid loss (diarrhea and vomiting).
699
# **Question:**
What is distributive or vasogenic shock?
Inadequate tissue perfusion when there is a **general marked vasodilatations**, despite the blood volume remains the same.
700
# **Question:**
In which scenarios can distributive or vasogenic shock occur?
Can occur in scenarios of fainting,
anaphylaxis or sepsis.
701
# **Question:**
What is cardiogenic shock?
Inadequate tissue perfusion when there is an **inadequate cardiac output due to myocardial abnormalities**.
702
# **Question:**
When can cardiogenic shock occur?
Can occur in scenarios of myocardial infarction, heart failure or arrythmias.
703
# **Question:**
What is obstructive shock?
Inadequate tissue perfusion when there is an **inadequate cardiac output due to an obstruction** of the blood flow in the lungs or heart.
704
# **Question:**
When can obstructive shock occur?
Can occur in scenarios of tension pneumothorax, pulmonary embolism, cardiac tumor or pericardial tamponade.
705
# **Complete the sentence:**
Circulatory shock occurs when there is a ____________ (hyperperfusion/hypoperfusion) of tissues, usually accompanied by ________________ (hypertension/hypotension) and ________________ (tachycardia/bradycardia).
hypoperfusion, hypotension, tachycardia
706
# **Question:**
Which of the types of circulatory shock presents a normal or high cardiac output?
Distributive or vasogenic shock
707
# **Complete the sentence:**
Distributive or vasogenic shock usually presents with a ____ (high/low) cardiac output, while hypovolemic, cardiogenic and obstructive shocks present with a ____ (high/low) cardiac output.
high, low
708
# **Question:**
Why are lactate levels usually elevated in patients suffering a circulatory shock?
In circulatory shock, tissue hypoperfusion leads to insufficient oxygen delivery to cells. This forces cells to switch from aerobic metabolism to anaerobic glycolysis, which generates lactate as a byproduct. The accumulation of lactate indicates tissue hypoxia and impaired oxidative metabolism.
709
# **Quetion:**
Why is high sodium intake a risk factor for hypertension?
High sodium intake increases water retention, leading to higher blood volume and increased cardiac output. It also enhances vascular resistance by promoting vasoconstriction and reducing endothelial function. These effects contribute to sustained high blood pressure and increase the risk of hypertension.
710
# **Question:**
What are the differences between the cricoid cartilage and the tracheal cartilages?
Both the cricoid cartilage and the tracheal cartilages are cartilages that surround the trachea, which is the beginning of the tracheobronchial tree.
However, while the tracheal cartilages are C-shaped (incomplete) rings, the cricoid cartilage is the only complete ring of cartilage around the trachea.
711
# **Complete the sentence:**
The tracheobronchial tree begins at the ________ and bifurcates at the ________ into the left and right ________, which continue to divide into smaller ________.
trachea, carina, bronchi, bronchioles
712
# **Complete the sentence:**
The lungs are divided in ________, which are separated by ________.
lobes, fissures
713
# **Question:**
What is the pleura?
The pleura are two flattened closed sacs made of serous membranes filled with pleural fluid, each one surrounding each lung.
714
# **Complete the sentence:**
Intrapleural pressure is usually ________ (positive/negative).
negative
715
# **Question:**
What does a negative intrapleural pressure mean?
It means that the intrapleural pressure is lower than the atmospheric pressure.
716
# **Question:**
What is a pneomothorax?
A pneumothorax is when air gets inside the chest cavity and creates pressure against the lungs, causing it them to collapse partially or fully.
717
# **Question:**
Why does difficulty breathing caused by an open pneumothorax worsen the condition?
If a patient has difficulty breathing, they will probably try to breathe in deeply and that will actually lead to more air entering the lungs and the chest cavity, aggravating the collapse.
718
# **Question:**
What is the main function of the respiratory system?
To guarantee the introduction of oxygen (O2) into the blood and the removal of carbon dioxide (CO2).
719
# **Question:**
What are the four main acessory functions of the respiratory system?
1. Olfaction of volatile molecules (and distinguishing pleansant and unpleasant smells)
2. Speech production
3. Acid-base balance
4. Synthesis of vasoactive substances
720
# **Question:**
What is the role of carbon anhydrase in acid base balance?
It's an enzyme that helps convert carbon dioxide into bicarbonate and protons, helping to regulate pH.
721
# **Question:**
Why does hyperventilation increase the pH?
Hyperventilation increases the pH of the blood because breathing too fast removes too much carbon dioxide (CO₂), decreasing the CO₂ partial pressure. Since CO₂ reacts with water in the blood to form carbonic acid (H₂CO₃), less CO₂ means less acid. This makes the blood less acidic (more alkaline), increasing the pH.
722
# **Question:**
Why does hypoventilation decrease the pH?
Hypoventilation decreases the pH of the blood because breathing too slowly (e.g., in case of difficulty breathing) causes CO₂ to build up in the body. More CO₂ reacts with water in the blood to form carbonic acid (H₂CO₃), which releases hydrogen ions (H⁺). This makes the blood more acidic, lowering the pH.
723
# **Question:**
What is the name of excessive CO₂ in the body?
Hypercapnea
724
# **Question:**
What is the role of the respiratory system in the synthesis of Angiotensin II?
The Angiotensin converting enzyme (ACE) is produced by vascular endothelial cells throughout the body, but especially in the lungs. And ACE is responsible for converting Angiotensin I in Angiotensin II, a vasoconstrictor hormone.
725
# **Complete the sentence:**
In inspiration, the atmospheric pressure is ________ (lower/higher) than the intrapulmonary pressure, allowing for air inflow. Therefore, inspiration requires a ________ (positive/negative) pressure.
higher
726
# **Complete the sentence:**
In expiration, the atmospheric pressure is ________ (lower/higher) than the intrapulmonary pressure, allowing for air outflow. Therefore, expiration requires a ________ (positive/negative) pressure.
lower, negative
727
# **Complete the sentence:**
Inspiration involves the ____________ (contraction/relaxation) of the inspiratory muscles, contrarly to expiration.
contraction
728
# **Question:**
What is the the lung surfactant, where is it produced and what's its role?
Lung surfactant is a thin film of lipids and proteins that lines the lungs' alveoli, produced by the pneumocytes type II (a type of alveolar cells). The lung surfactant prevents the collapse of smaller alveoli.
729
# **Question:**
What is alveolar ectasia? What are the cause and complications?
Alveolar ectasia is a condition where the air sacs in the lungs are abnormally dilated (enlarged). This condition can result from structural weakness in the alveolar walls, often due to chronic lung diseases or aging-related loss of elasticity. Enlarged alveoli may reduce the surface area available for oxygen and carbon dioxide exchange, leading to lower oxygen levels in the blood (hypoxemia) and less efficient gas exchange (since the air prefers to go to larger alveoli, even though they are less efficient for gas exchange).
730
# **Question:**
What is the ideal ventilation/perfusion (V/Q) ratio?
The ideal ventilation/perfusion ratio is V/Q = 1, since ideally ventilation would be equivalent to perfusion.
731
# **Question:**
In what lung region is there an evident ventilation/perfusion ratio (V/Q) mismatch (i.e., very different from 1)?
In the apex of the lung, since there is limited perfusion compared with ventilation.
732
# **Question:**
What are the 2 main receptors and the 2 main reflexes involved in the regulation of breathing?
Receptors:
* Peripheral receptors (pO₂ and pCO₂)
* Central receptors (pCO₂ and pH)
Reflexes:
* Chemoreflex
* Hering-Breuer reflex
733
# **Question:**
What is the Hering-Breuer reflex?
It's a reflex triggered to **prevent the over-inflation of the lung**. Pulmonary stretch receptors present on the wall of bronchi and bronchioles of the airways respond to excessive stretching of the lung during large inspirations.
734
# **Question:**
What activates the chemoreflex?
The chemoreflex is activated by hypoxia (low pO₂) or hypercapnea (high pCO₂).
735
# **Question:**
What happens when the chemoreflex is activated?
The activation of the chemoreflex induces:
* Tachypnea
* Tachycardia
* Vasoconstriction
736
# **Question:**
What are two ways of mechanical breathing/ventilation?
**Positive Pressure Ventilation** is when air is pushed into the lungs using external force, for example: **Tracheal Intubation** and **Tracheostomy**.
**Negative Pressure Ventilation** is when air is pulled into the lungs by creating a vacuum around the chest, simulating normal breathing and mimicking natural diaphragm movement. For example, the **Iron Lung** (used for polio patients in the past) is a chamber around the chest reduces pressure, expanding the lungs and drawing in air.
737
# **Question:**
Give examples of diagnostic tests and exams for the respiratory system.
* Lung Function tests (e.g., spirometry)
* Exercise stress test (e.g., treadmill)
* Arterial gasimetry
* Pulse oximetry
* Chest X-ray
* Bronchoscopy
* Microbial cultures
738
# **Question:**
Distinguish type 1 and type 2 respiratory failure.
Respiratory failure type 1 is also called hypoxemic respiratory failure and is characterized by hypoxia, i.e., a decrease in pO₂ in peripheral blood.
Respiratory failure type 2 is also called hypercapnic respiratory failure and is characterized by hypercapnea, i.e., an increase in pCO₂ in peripheral blood.
739
# **Question:**
How can a type 2 respiratory failure (hypercapnic respiratory failure) present without acidemia?
A type 2 respiratory failure corresponds to hypercapnea (increased pCO₂). More CO₂ reacts with water in the blood to form carbonic acid (H₂CO₃), which releases hydrogen ions (H⁺). Therefore, there is more acid production, which lowers the pH, possibly resulting in acidemia. **However, this acidemia might be compensated by the kidney, which might be retaining bicarbonate (HCO₃⁻) to maintain pH homeostasis.**
740
# **Question:**
What are the 3 main causes of respiratory failure?
* **Ventilation dysfunction:** caused by obstruction of the respiratory tract, muscle weakness or paralysis or trauma to the thoracic wall.
* **Ventilation/Perfusion Ratio mismatch:** caused by chronic obstructive lung disease (COPD), restrictive lung disease, lung infections pr vascular lung disease.
* **Hematosis dysfunction:** caused by pulmonary edema.
741
# **Question:**
What are the 4 main types of Obstructive Lung Disease?
* Asthma
* Chronic Bronchitis
* Emphysema
* Chronic Obstructive Lung Disease (COPD)
742
# **Question:**
What is obstructive lung disease?
It's the partial or irreversible obstruction of the lower airways.
743
# **Question:**
Asthma is a type of ________ (reversible/irreversible) of obstructive lung disease.
reversible
744
# **Question:**
What is Asthma?
It's a disease of airway inflammation and airflow obstruction.
745
# **Question:**
What are the main symptoms of Asthma?
* Wheezing
* Chest tightness
* Dyspnea
* Cough
* Bronchial hyperresponsiveness
746
# **Question:**
Distinguish intrinsic and extrinsic Asthma.
Extrinsic asthma usually presents at a younger age and is less severe, since it is linked with **hypersensitivity reactions and atopy** (tendency to produce an exaggerated immunoglobulin E immune response), normally triggered by **allergerns**.
Intrinsic asthma normally appears later in life and is associated with a greater severity, mainly due to the lack of an obvious cause, since it presents an apparent **lack of atopy** and **non-allergic triggers**.
747
# **Question:**
Are tachypnea and tachycardia always present in asthma?
No, they are usually absent in mild disease but present in acute exacerbations.
748
# **Question:**
What are the two types of lung disease?
Obstructive and Restrictive
749
# **Question:**
What is the first physiological event in asthma that leads to hypoxemia and respiratory acidosis?
Airway obstruction.
750
# **Questão:**
How does airway obstruction affect the ventilation/perfusion (V/Q) ratio?
It decreases the V/Q ratio, leading to inadequate ventilation in certain lung areas.
751
# **Question:**
What happens to oxygen (O₂) and carbon dioxide (CO₂) levels in severe asthma?
O₂ decreases (hypoxemia) and CO₂ increases (hypercapnia), leading to respiratory acidosis.
752
# **Question:**
How does the body respond to hypoxemia and hypercapnia in severe asthma?
By activating the chemoreflex, which induces tachypnea, tachycardia and vasoconstriction.
753
# **Question:**
What are the effects of the chemoreflex in asthma?
Increased respiratory rate (tachypnea) and increased heart rate (tachycardia).
754
# **Question:**
What are the two main categories of allergens that trigger extrinsic asthma?
* **Low-molecular weight chemicals** (e.g., drugs, isocyanate, anhydrides, chromate)
* **Complex organic molecules** (e.g., animal danders, dust mites, enzymes, wood dusts)
755
# **Question:**
What types of drugs can trigger asthma symptoms?
Beta blockers and NSAIDs.
756
# **Question:**
Name two physiologic and pharmacologic mediators of smooth muscle that can trigger asthma.
Histamine and ATP.
757
# **Question:**
What are some physicochemical agents that can trigger asthma?
* Exercise, hyperventilation with cold, dry air
* Air pollutants
* Viral infections (e.g., Influenza A)
758
# **Question:**
What are the two phases of an asthma response to a trigger?
* **Early response:** occurs within **10-15 minutes**
* **Late response:** occurs within **4-8 hours**
759
# **Question:**
What are the main causes of cough in asthma?
* Airway narrowing
* Mucus hypersecretion
* Neural hyperresponsiveness
760
# **Question:**
What is the primary cause of wheezing in asthma?
Caliber reduction leading to turbulent airflow.
761
# **Question:**
Does wheezing correlate well with the severity of airway narrowing?
No.
762
# **Question:**
What are the three main causes of dyspnea and chest tightness in asthma?
* **Decreased lung compliance** → increased muscular effort
* **Airway obstruction** → thoracic distension, hypoxia, hypercapnia
* **Hypoxia and hypercapnia** → increased respiratory rate and depth
763
# **Question:**
How does airway obstruction contribute to dyspnea?
It leads to thoracic distension, hypoxia, and hypercapnia, increasing respiratory effort.
764
# **Question:**
What causes increased inspiratory effort in asthma?
* Increased airway resistance
* Decreased O₂ levels (hypoxemia)
* Increased CO₂ levels (hypercapnia)
765
# **Question:**
How does increased inspiratory effort affect venous return in pulsus paradoxus?
Increased inspiratory effort → Increased venous return to the right heart → Increased right ventricular filling.
766
# **Question:**
What is pulsus paradoxus in asthma?
A decrease in blood pressure during inspiration due to increased airway resistance and altered cardiac dynamics.
767
# **Question:**
What happens to the interventricular septum during pulsus paradoxus?
The interventricular septum deviates to the left due to increased right ventricular filling.
768
# **Question:**
How does pulsus paradoxus affect the left ventricle?
* Decreased left ventricular filling
* Decreased left ventricular ejection
769
# **Question:**
Why does increased airway resistance contribute to pulsus paradoxus?
Increased airway resistance forces the patient to generate a stronger inspiratory effort, altering intrathoracic pressure and cardiac filling dynamics.
770
# **Question:**
How does increased right ventricular filling affect the left heart during pulsus paradoxus?
The right ventricle expands more than usual, making the interventricular septum shift to the left, which reduces left ventricular filling. Consequently, cardiac output and arterial pulse decrease during inspiration.
771
# **Question:**
Why is pulsus paradoxus clinically significant in asthma?
It is a sign of severe airway obstruction and can indicate impending respiratory failure, requiring urgent intervention.
772
# **Question:**
What is chronic bronchitis?
Chronic bronchitis is a chronic airway inflammation with subsequent obstruction. It's a type of chronic obstructive pulmonary disease (COPD).
773
# **Question:**
What is Chronic obstructive pulmonary disease (COPD)?
Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by progressive airflow limitation and tissue destruction in the airways and/or lung.
774
# **Question:**
What are the top three causes for COPD?
* Cigarette smoking
* Genetic susceptibility
* Alpha-1 protease inhibitor deficiency
775
# **Question:**
What is the leading cause of COPD?
Cigarette smoking
776
# **Question:**
Is age a risk factor of COPD?
Yes, COPD typically begins in the adult age.
777
# **Complete the sentence:**
One of the clinical manifestations of chronic bronchitis is ________ (pink puffer/blue bloater).
blue bloater
778
# **Complete the sentence:**
One of the clinical manifestations of pulmonary emphysema is ________ (pink puffer/blue bloater).
pink puffer
779
# **Question:**
What are the characteristics of a productive cough in chronic bronchitis?
* Thick sputum (contains free DNA from lysed cells)
* Purulent sputum (suggests bacterial infection)
* Hemoptysis (due to damaged mucosa)
* Less effective in clearing sputum
* Duration of at least 3 months in 2 consecutive years
780
# **Question:**
What happens to the mucosa, the mucus-secreting glands and the bronchial wall in chronic bronchitis?
* Inflamed and edematous mucosa
* Hypertrophy and hyperplasia of mucus-secreting glands
* Fibrosis and thickening of the bronchial wall
781
# **Question:**
What causes wheezing in chronic bronchitis?
Persistent airway narrowing due to inflammation and mucus obstruction.
782
# **Question:**
What causes crackles in chronic bronchitis?
Increased mucus production leading to airflow obstruction and turbulence in the airways.
783
# **Question:**
What is the Blue Bloater phenotype in chronic bronchitis?
* Cyanosis (blue) due to chronic hypoxia
* Obesity and fluid retention (bloater) due to right heart failure (cor pulmonale)
784
# **Question:**
Why does chronic bronchitis lead to hypoxia and hypercapnia?
Mucus plugging and airway obstruction cause ventilation-perfusion (V/Q) mismatch. This reduces oxygen exchange, leading to hypoxia (low O₂) and hypercapnia (high CO₂).
785
# **Question:**
How does fibrosis contribute to airway obstruction in chronic bronchitis?
Fibrosis thickens the bronchial walls, making the airways less flexible and more resistant to airflow.
786
# **Question:**
Why does tachycardia occur in acute hypoxic exacerbations of chronic bronchitis?
Increased airway obstruction decreases the V/Q ratio, inducing hypoxia (↓O₂) and hypercapnia (↑CO₂) and, thus, resulting in respiratory acidosis. This activates the chemoreflex, which triggers tachycardia (increased heart rate), tachypnea and vasoconstriction (increased pulmonary resistance).
787
# **Question:**
How does chronic hypoxia lead to right heart failure in chronic bronchitis?
Hypoxia (↓O₂) and hypercapnia (↑CO₂) trigger pulmonary vasoconstriction, due to activation of the chemoreflex. Consequently, an increased pulmonary resistance (increased resistance in the pulmonary circulation that enters the right side of the heart) puts strain on the right ventricle, leading to right heart failure (cor pulmonale).
788
# **Question:**
What are the clinical signs of right heart failure in chronic bronchitis?
* Jugular venous distension (due to increased central venous pressure)
* Peripheral edema (fluid retention in lower limbs)
* Hepatomegaly (congestion of the liver due to right heart failure)
789
# **Question:**
How does chronic hypoxia cause polycythemia in chronic bronchitis?
Low oxygen levels (↓O₂) stimulate erythropoietin secretion from the kidneys, which promotes erythropoiesis (red blood cell production). An increased number of red blood cells results in an increased hematocrit (polycythemia), which improves oxygen-carrying capacity.
790
# **Complete the sentence:**
Chronic bronchitis, Pulmonary emphysema and Asthma are all types of ________.
Chronic obstructive lung disease (COPD)
791
# **Question:**
What is Pulmonary Emphysema?
Emphysema is a progressive chronic lung condition in which the alveolar septal walls are destroyed, leading to permanently dilated and inflated alveoli.
792
# **Question:**
What are the major contributive factors to emphysema?
* Genetic defects (e.g., α1-antitrypsin deficiency)
* Smoking (induces oxidative stress and protease activity)
* Bacterial colonization (chronic inflammation damages alveoli)
793
# **Questions:**
What are the three key pathophysiological changes in emphysema?
1. **Destruction of alveoli walls** → Progressive ventilatory dysfunction
2. **Increased air trapping** → ↑ Residual volume
3. **Lung hyperinflation** → Reduced elastic recoil
794
# **Question:**
Does emphysema lead to compensatory anatomical changes?
Yes.
* Rectilinization of the ribcage → Increased PA (anteroposterior) diameter ("barrel chest")
* Flattening of the diaphragm due to hyperinflation
795
# **Question:**
What are the clinical signs of emphysema?
* **Dyspnea** (due to impaired gas exchange)
* **Tachycardia** (during acute hypoxic exacerbations)
* **Right heart failure** (if hypoxia is chronic)
796
# **Question:**
Why are emphysema patients called "pink puffers"?
* Mild hypoxemia with preserved oxygenation → Pink skin
* Increased respiratory effort ("puffing") to compensate for alveolar damage
797
# **Question:**
How does emphysema affect ventilation/perfusion ratio (V/Q)?
Emphysema increases the ventilation/perfusion ratio (V/Q) due to the destruction of alveolar walls and the loss of capillaries.
798
# **Question:**
Why does emphysema lead to a compensatory increase in minute ventilation?
The destruction of alveolar walls in emphysema reduces gas exchange efficiency, prompting a compensatory increase in minute ventilation to maintain normal O₂ and CO₂ levels.
799
# **Question:**
What is the consequence of a high ventilation/perfusion (V/Q) ratio in emphysema?
A high V/Q ratio in emphysema can lead to poor matching of ventilation and perfusion, which makes gas exchange less efficient.
800
# **Question:**
How does the compensatory increase in minute ventilation help in emphysema?
The increase in minute ventilation helps maintain normal oxygen (O₂) and carbon dioxide (CO₂) levels despite reduced efficiency in gas exchange.
801
# **Question:**
What are restrictive lung diseases?
Group of diseases characterized by a **widespread lung fibrosis**, leading to decreased lung compliance and to a **decreased total lung capacity**.
802
# **Question:**
What are the main causes of pulmonary fibrosis?
* Granulomatous (e.g. Sarcoidosis)
* Pneumoconiosis
* Inherited
* Idiopathic pulmonary fibrosis
* Collagen-vascular and pulmonary renal syndromes
* Other (dystrophies, skeletal and neurological disorders)
803
# **Question:**
What is idiopathic pulmonary fibrosis?
Infiltration of inflammatory cells and fluid in the lung parenchyma leading to scarring and fibrosis, without a known causative agent.
804
# **Question:**
What is the first step in the progression of Idiopathic Pulmonary Fibrosis?
The first step is tissue injury, where the lung tissue is damaged, initiating the inflammatory and fibrotic process.
805
# **Question:**
How does increased capillary permeability contribute to Idiopathic Pulmonary Fibrosis?
Increased capillary permeability allows fluid and proteins to leak into the alveolar space, promoting inflammation and further tissue damage.
806
# **Question:**
What is the role of epithelial injury in the development of Idiopathic Pulmonary Fibrosis?
Epithelial injury disrupts the integrity of the alveolar lining, triggering inflammation and fibroblast activation, which contribute to fibrosis.
807
# **Question:**
How do leucocytes contribute to Idiopathic Pulmonary Fibrosis?
Leucocyte influx and proliferation occur in response to tissue injury, amplifying the inflammatory response and promoting the release of cytokines that stimulate fibrosis.
808
# **Question:**
What happens after leucocyte influx in the progression of Idiopathic Pulmonary Fibrosis?
After leucocyte influx, further tissue injury occurs, followed by tissue remodelling and fibrosis, leading to scarring of the lung tissue and impaired lung function.
809
# **Question:**
What are the five main steps involved in Idiopathic Pulmonary Fibrosis?
1. Tissue injury
2. Increased capillary permeability
3. Epithelial injury
4. Leucocyte influx and proliferation
5. Further tissue injury, remodelling and fibrosis
810
What are common symptoms of Idiopathic Pulmonary Fibrosis (IPF)?
Common symptoms include:
* chronic cough
* dyspnea (shortness of breath)
* tachypnea (rapid breathing)
* inspiratory crackles
* digital clubbing
811
# **Question:**
How does idiopathic pulmonary fibrosis lead to tachypnea?
Fibrosis causes a thickening of the capillary-alveolar barrier, leading to impaired gas exchange and hypoxia (low oxygen levels), which triggers tachypnea (increased respiratory rate) as the body attempts to compensate for reduced oxygen.
812
# **Question:**
How does idiopathic pulmonary fibrosis lead to dyspnea (shortness of breath)?
Fibrosis stiffens the lung tissue, reducing its ability to expand and contract properly, which decreases lung compliance (the ability of the lungs to stretch and expand during breathing). Decreased lung compliance makes the lungs stiffer, requiring greater effort to expand with each breath, leading to an increased work of breathing and causing dyspnea (difficulty breathing).
813
# **Question:**
What causes inspiratory crackles in Idiopathic Pulmonary Fibrosis patients?
Inspiratory crackles occur due to the opening of collapsed alveoli during inspiration, which is a hallmark sign of Idiopathic Pulmonary Fibrosis.
814
# **Question:**
What causes dyspnea and tachypnea in Idiopathic Pulmonary Fibrosis?
Dyspnea and tachypnea in IPF are caused by fibrosis, which thickens the capillary-alveolar barrier, leading to hypoxia (low oxygen levels) and increased respiratory effort.
815
# **Question:**
How does decreased lung compliance affect patients with Idiopathic Pulmonary Fibrosis?
Decreased lung compliance results in stiffer lungs, requiring increased respiratory effort, which causes dyspnea (shortness of breath).
816
# **Question:**
Why does digital clubbing occur in Idiopathic Pulmonary Fibrosis?
Digital clubbing, a widening of the fingertips, occurs in IPF due to chronic hypoxia, which leads to changes in the blood vessels and soft tissues of the fingers and toes.
817
# **Question:**
How does the body compensate for the hypoxia caused by fibrosis in Idiopathic Pulmonary Fibrosis?
In response to hypoxia, the body increases the respiratory rate (tachypnea) in an attempt to deliver more oxygen to the tissues.
818
# **Question:**
What is Pneumoconiosis?
Pneumoconiosis is a group of interstitial lung diseases caused by prolonged occupational or environmental exposure to inhalation of dust particles, leading to lung damage and interstitial fibrosis. It affects miners, builders, and other workers who breathe in certain kinds of dust on the job.
819
# **Question:**
How does pneumoconiosis develop over time?
It develops through long-term inhalation of dust particles, which causes inflammation of the lung parenchyma (lung tissue) and gradual destruction of connective tissue.
820
# **Quesion:**
What is the typical onset of pneumoconiosis symptoms?
The disease typically has an **insidious onset**, with dyspnea (shortness of breath) being the first symptom to appear.
821
# **Question:**
What happens to the lung tissue in pneumoconiosis?
In pneumoconiosis, continuous exposure to dust particles leads to inflammation and progressive damage to lung tissue, resulting in fibrosis and scarring.
822
# **Question:**
What are common examples of pneumoconiosis?
Common examples include **asbestosis**, caused by asbestos exposure, and **silicosis**, caused by inhaling silica dust.
823
# **Question:**
What are pulmonary vascular diseases (or vascular lung diseases)?
Pulmonary vascular disease is a term for a group of conditions that affect the blood vessels in the lungs.
824
# **Question:**
What is the main type of pulmonary vascular disease?
Acute pulmonary embolism
825
# **Question:**
What are the possible causes of acute pulmonary embolism?
It can be caused by:
* Thrombi (thromboembolism)
* Gas (e.g., surgery, central venous catheters)
* Tumor cells (e.g., renal carcinoma with inferior vena cava invasion)
* Oil (e.g., lymphangiography)
* Fat (e.g., trauma)
* Liquid (e.g., amniotic fluid)
* Parasite eggs (e.g., schistosomiasis)
826
# **Question:**
What is the main consequence of large thrombi or multiple small thrombi in acute pulmonary embolism?
Large or multiple small thrombi can lead to **vascular occlusion**, which prevents blood flow to the lungs.
827
# **Question:**
Where do thrombi that cause pulmonary embolism usually originate?
Thrombi commonly originate from:
* Popliteal veins
* Femoral veins
* Iliac veins
* Upper limbs (e.g., from catheters)
* Right heart chambers (e.g., from pacemaker wires)
828
# **Question:**
What are the two main risk factors for pulmonary embolism?
* **Increased venous stasis:** immobilization, heart failure, pregnancy, obesity, blood hyperviscosity, vascular lesions, advanced age
* **Increased coagulability:** tissue trauma (surgery, trauma, myocardial infarction), malignancy, nephrotic syndrome, oral contraception, genetic disorders
829
# **Question:**
What are the hemodynamic changes in pulmonary embolism?
Hemodynamic changes in pulmonary embolism include:
* Increased pulmonary vascular resistance
* Increased pressure in the pulmonary trunk
* Increased strain on the right ventricle
830
# **Question:**
How does the ventilation/perfusion (V/Q) ratio change in pulmonary embolism?
Changes in the V/Q ratio include:
* Increased V/Q mismatch
* Decreased CO₂ excretion and accumulation
* Compensatory hyperventilation
* Hypoventilation leading to type II pneumocyte dysfunction
* Loss of surfactant causing edema, alveolar collapse, and atelectasis
* In perfused alveoli, decreased V/Q ratio
* Hypoxemia
831
# **Question:**
What is the clinical presentation of a small pulmonary embolism?
Small emboli typically present with pleuritic pain, cough, and dyspnea.
832
# **Question:**
What is the clinical presentation of a large pulmonary embolism?
Large emboli present with pleuritic pain, tachypnea, dyspnea, hemoptysis, fever, and hypoxia.
833
# **Question:**
What is the clinical presentation of a massive pulmonary embolism?
Massive emboli present with pleuritic pain, hypotension, and loss of consciousness.
834
# **Question:**
How does hypoventilation affect type II pneumocytes in the lungs?
Hypoventilation occurs in areas of the lung that are not receiving sufficient perfusion (blood flow) due to the embolism. The lack of adequate ventilation leads to type II pneumocyte dysfunction. Type II pneumocytes are responsible for producing surfactant, which prevents alveolar collapse by reducing surface tension in the lungs. Dysfunction leads to impaired surfactant production.
835
# **Question:**
What is the role of surfactant in the lungs?
Surfactant reduces surface tension in the alveoli, helping to keep them open and preventing alveolar collapse during exhalation. It is essential for maintaining normal lung function.
836
# **Question:**
What happens when there is a loss of surfactant in pulmonary embolism?
Loss of surfactant results in increased surface tension, leading to alveolar collapse, reduced gas exchange, and the development of pulmonary edema.
837
# **Question:**
What is alveolar collapse, and how does it occur in pulmonary embolism?
Alveolar collapse occurs when the small air sacs (alveoli) in the lungs deflate due to the lack of surfactant, causing impaired gas exchange and contributing to atelectasis (lung tissue collapse).
838
# **Question:**
What is atelectasis and how is it related to pulmonary embolism?
Atelectasis is the partial or complete collapse of lung tissue. In pulmonary embolism, it occurs due to the loss of surfactant and alveolar collapse, leading to decreased ventilation in the affected areas.
839
# **Complete the sentence:**
In acute pulmonary embolism, the ventilation/perfusion ratio is ________ (increased/decreased).
increased
| (due to reduced perfusion)
840
# **Question:**
Why is the V/Q ratio increased in acute pulmonary embolism?
In Pulmonary Embolism, a blockage in the pulmonary arteries (due to thrombi, fat, gas, etc.) leads to reduced blood flow (perfusion) to certain areas of the lungs, while ventilation (airflow) to those areas remains unchanged or even increases as a compensatory mechanism.
841
# **Question:**
Why is there a compensatory hyperventilation in pulmonary embolism?
As perfusion to parts of the lungs is impaired (due to embolism), less blood can pick up CO₂ from the tissues. This leads to a **reduced ability to excrete CO₂**, resulting in its accumulation in the bloodstream, a condition known as **hypercapnia**.
In response to the accumulation of CO₂ (and the decreased oxygen levels from impaired gas exchange), the body compensates by hyperventilating (rapid, deep breathing). This is an attempt to expel excess CO₂ and increase oxygen intake.
842
# **Question:**
Why is there a decreased V/Q ratio in perfused alveoli in pulmonary embolism?
In areas where perfusion (blood flow) is still intact but ventilation is impaired (due to alveolar collapse or hypoventilation), the V/Q ratio decreases. This is because blood flow is still going to these areas, but the lack of airflow (due to collapsed or poorly ventilated alveoli) means that these areas are less efficient at oxygenating the blood.
843
The GI tract includes the pathway that connects the ________ to the ________.
mouth, anus
844
What are the 4 main functions of the GI system?
* Digestion
* Secretion
* Motility
* Absorption
845
What organs belong to the upper GI tract?
* Mouth
* Esophagus
* Stomach
846
What organs belong to the lower GI tract?
* Small intestine
* Large intestine
* Anus
847
What are the 6 parts of the large intestine?
1. Cecum
1. Ascending colon
1. Transverse colon
1. Descending colon
1. Sigmoid colon
1. Rectum
848
What are the 3 parts of the small intestine?
1. Duodenum
1. Jejunum
1. Ileum
849
What other organs and glands (besides the upper and lower GI tract) belong to the GI system?
* Liver
* Pancreas
* Gallbladder
* Salivary glands
850
Give examples of pathologies in the upper GI tract.
* Gastritis
* Esophageal achalasia (the muscles in the esophagus don't relax)
* Peptic ulcer
* Gastroesophageal reflux
851
Give examples of pathologies in the lower GI tract.
* Diarrhea
* Constipation
* Inflammatory bowel disease
* Diverticular disease
* Irritable bowel syndrome
852
Give examples of pathologies in the other organs and glands that belong in the GI system.
* Cholelithiasis (gallstones, i.e., hardened pieces of bile that form in your gallbladder or bile ducts)
* Cirrhosis (advanced scarring of the liver)
* Hepatitis
* Liver carcinoma
853
What is gastroesophageal reflux disease (GERD)?
It is characterized by passage of gastric contents into the
esophagus.
854
What are the two types of gastrointestinal reflux disease? What is the most common?
Can be divided into gastroesophageal reflux
* Without esophageal erosion (~70% of patients).
* With esophageal erosion = reflux esophagitis (30%).
855
What are the two main causes of gastrointestinal reflux disease?
* Gastroesophageal junction dysfunction (dysfunction of the lower esophageal sphincter, which allows reflux of gastric contents into the esophagus)
* Decreased acid elimination
856
What are the four main causes of gastroesophageal junction dysfunction?
1. Increased frequency of cardia relaxations
1. Reflux associated with cardia relaxations
1. Mechanical dysfunction of the cardia
1. Increased intragastric pressure
857
What are the two main causes of decreased acid elimination?
* Decreased saliva secretion
* Decreased peristalsis (involuntary muscle movement that moves food through your gastrointestinal tract)
858
What is the main cause of decreased saliva secretion?
Smoking
859
What are common food triggers of GERD?
Spicy foods, alcohol, fatty foods, and junk foods.
860
What are the two main causes of the mechanical dysfunction of the cardia?
* Hiatal hernia (occurs when the upper part of the stomach bulges through the diaphragm into the chest cavity)
* Neoplasia
861
What are the three main causes of increased intragastric pressure?
* Pregnancy
* Obesity
* Delayed gastric emptying
862
How does smoking contribute to GERD?
Smoking relaxes the lower esophageal sphincter (LES), increasing the risk of acid reflux and symptoms like heartburn and chest pain.
863
What is abnormal LES relaxation?
It is excessive or prolonged transient lower esophageal sphincter relaxation, which allows stomach acid to move into the esophagus.
864
What factors increase intra-abdominal pressure and worsen GERD?
Exercise, obesity, and positional changes (e.g., lying down).
865
How does delayed gastric emptying contribute to GERD?
Gas buildup in the stomach increases pressure on the cardia, which is sensed by pressure receptors, stimulating the vagus nerve, which leads to the lower esophageal sphincter relaxation, allowing acid to reflux into the esophagus.
866
What medication used for hypertension can worsen GERD?
Amlodipine, which is a calcium channel blocker. Calcium channels allow calcium ions flow into the muscle cell, causing the muscle to contract. By blocking these channels, Amlodipine impairs the lower esophageal sphincter from contracting, leading to its relaxation and, thus, to acid reflux.
867
What complications arise from repeated esophageal damage in GERD?
* Metaplasia (replacement of squamous epithelium with columnar cells)
* Barrett’s Esophagus (precancerous lesion)
* Adenocarcinoma (progression of Barrett’s Esophagus)
* Esophageal scarring and bleeding
* Mechanical dysphagia (difficulty swallowing solid foods)
868
What is Non-Erosive Reflux Disease (NERD)?
It's a form of GERD where heartburn persists despite treatment, but without visible esophageal damage.
869
What are the respiratory complications of GERD?
* Water regurgitation (water brash, which occurs when spit and stomach acid mix together and cause a sour taste)
* Aspiration of acid into the larynx and lungs
* Upper respiratory tract irritation
* Chronic cough (especially at night)
* Asthma
* Hoarse voice (rough voice, typical of a sore throat)
870
What are the 7 most frequent clinical manifestations of GERD?
1. Epigastric pain with a burning feeling
2. Regurgitation (vomiting)
3. Dysphagia (difficulty in swallowing)
4. Odynophagia (pain while swallowing)
5. Sialorrhea (excess saliva)
6. Halitosis (bad breath)
7. Teeth damage (due to gastric acid in mouth)
871
What are the 5 less frequent clinical manifestations of GERD?
1. Eructation (burping)
2. Bloating (sensation of so tightness due to fluid or gas accumulation)
3. Nausea
4. Anorexia
5. Chronic cough
872
What are the main triggers (e.g., factors and behaviours) that exacerbate symptoms in GERD?
* Lying down after meals or at night
* Bending over
* Intake of fluids with meals
* Intake of certain foods and drinks (Ex. Caffein, alcohol, fatty foods or spicy foods)
* Smoking
873
What are the 6 main complications of GERD?
1. Ulcer on the esophagus
2. Scarring and narrowing of the esophagus
3. Esophagitis
4. Changes in the esophagus cells linen (e.g., Barrett’s esophagus)
5. Asthma
6. Esophagus carcinoma
874
What are the main diagnostic methods for GERD?
* Anamnesis
* Physical examination
* Biochemical blood tests
* Endoscopy
* Esophagram
* Esophageal pH test
* Esophageal manometry
* CT or MRI
875
What is an endoscopy, and how is it used in GERD diagnosis?
Endoscopy involves inserting a flexible tube with a camera down the throat to visualize the esophagus and check for damage, inflammation, or Barrett’s esophagus.
876
What is an esophagram, and why is barium used?
An esophagram (also called a barium swallow/enema) is an X-ray of the esophagus where barium contrast helps highlight abnormalities like reflux or abnormal narrowings.
877
What does an esophageal pH test measure and why is it used in GERD diagnosis?
It records the pH level in the esophagus over 24 hours to determine acid exposure and diagnose GERD.
878
What is esophageal manometry, and why is it performed in GERD diagnosis?
It measures pressure and movement in the esophagus to evaluate the function of the lower esophageal sphincter (LES) and esophageal motility disorders, associated with GERD.
879
How can CT or MRI aid in GERD diagnosis? What are the most common findings?
These imaging techniques provide detailed views of the esophagus and surrounding structures.
In CT or MRI for GERD, we may see:
* Esophageal thickening (from inflammation or scarring)
* Hiatal hernia (if present, which can worsen reflux)
* Esophageal strictures (narrowing due to chronic acid exposure)
* Barrett’s esophagus (potential precancerous changes in the esophageal lining)
880
What are the most common findings in biochemical blood tests for GERD?
Possible findings include:
* low hemoglobin (if there is chronic bleeding from esophageal damage) and anemia
* elevated inflammation markers
881
What are the most common findings in an esophagram (barium swallow X-ray) for GERD?
* Reflux of barium back into the esophagus
* Esophageal strictures (narrowing due to acid damage)
* Hiatal hernia (if present)
882
What are the most common findings in an esophageal pH test for GERD?
* Low pH in the esophagus (acid reflux episodes)
* Prolonged acid exposure over 24 hours
* Worsening acidity when lying down or after meals
883
What are the most common findings in esophageal manometry for GERD?
* Weak lower esophageal sphincter (LES) (does not close properly)
* Abnormal esophageal motility (poor movement of food down the esophagus)
884
What is a peptic ulcer?
It is a lesion characterized by open sores in the inner lining of the gastric or duodenal mucosa that penetrates the muscularis mucosa layer.
885
Why is it called "**peptic**" ulcer?
“Peptic” means it’s related to digestion, as the word is derived from pepsin, the major digestive enzyme produced in the stomach.
886
What are the two main types of peptic ulcers? Which is more common?
* **Gastric ulcer (80%)**: typically in the lesser curvature, at the body-antrum transition.
* **Duodenal ulcer (20%)**: both at the anterior or posterior wall.
887
In what age and gender are peptic ulcers more common?
Middle-aged adults, male gender.
888
What is the cardia?
The part of the stomach that is closest to the esophagus.
889
What is are the two main causes of peptic ulcers?
| (Etiology)
* Infection with Helicobacter pylori (H. pylori) bacteria
* Long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs)
890
What are the other possible causes of peptic ulcers, beside H. pylori and NSAIDs?
| (Etiology)
* Corticosteroids
* Alcohol
* Tobacco
* Gastric hyperacidity
* Duodenal-gastric reflux
* Zollinger-Ellison syndrome (rare digestive disorder that occurs when tumors in the pancreas or small intestine cause the stomach to produce too much acid)
* Acute stress
* Malignancy
* Inflammatory diseases (e.g., Crohn's Disease)
891
How do peptic ulcers develop?
| (Pathophysiology)
Increased damage and/or impaired defense can lead to decreased mucus production, which exposes the inner lining of the gastric/intestinal mucosa to acid, leading to epithelial cell dead and open sores.
892
What are the normal protective factors present in the gastric and intestinal wall that prevent/repair damage?
* Surface mucus secretion
* Bicarbonate secretion into mucus (neutralizes acid)
* Mucosal blood flow (supports tissue repair)
* Epithelial barrier function
* Epithelial regenerative capacity
* Prostaglandins (stimulate mucus and bicarbonate production)
893
What are the harmful triggers that increase damage or impair defenses in peptic ulcer disease?
* H. pylori infection (produces urease, an enzyme that neutralizes acid and weakens the gastric lining)
* NSAID use (reduces prostaglandins)
* Tobacco & alcohol (increase acid, reduce mucus)
* Gastric hyperacidity
* Duodenal-gastric reflux
894
How does H. pylori contribute to peptic ulcer formation?
H. pylori bacteria, which is commonly present in the human stomach, can overgrow and colonize the gastric mucosa, by adhering to epithelial cells. These bacteria inhibits mucin protein synthesis, decreasing mucus production and dysrupting this protective layer of the inner lining of the gastric/intestinal mucosa. Additionally, H. pylori can produce urease, which elevates the pH, further damaging the mucosa and leading to ulcers.
In summary, H. pylori:
* Colonizes epithelial cells
* Decreases mucus production
* Increases acid exposure to the mucosa
895
What are the NIGS histological changes seen in peptic ulcers?
* Necrotic debris (N) (from epithelial cells death)
* Acute inflammation (I) (infiltration of neutrophils)
* Granulation tissue (G) (repair response)
* Fibrosis (S) (scar formation)
896
What are the most common clinical manifestations of peptic ulcers?
Peptic ulcers are often asymptomatic (in about 70% of the patients). However, some of the most common symptoms include:
* Epigastric pain with a burning sensation
* Indigestion
* Bloated stomach
* Burping
* Nausea and vomiting.
897
How do symptoms differ in gastric and in duodenal ulcers?
* In gastric ulcer, symptoms might worsen after food intake and felling night pain is common.
* In duodenal ulcer, symptoms might actually improve after food intake, and night pain is not as often.
898
What are the clinical manifestations of peptic ulcers associated with bleeding?
* Melena (blood in feces)
* Dizziness
* Pallor (paleness)
899
What are the 4 most common complications of peptic ulcers?
* Bleeding (most common)
* Perforation (life-threatening a tear in the stomach wall that allows gastric contents to leak into the peritoneal cavity, including acid and bacteria, which cause corrosion and infection)
* Fistulation (abnormal direct connection from the stomach to another organ, typically the colon or the gallbladder)
* Malignant evolution (which can cause obstruction of the GI tract by the mass)
900
What are the main diagnostic methods for peptic ulcers?
* Anamnesis
* Physical examination
* Biochemical blood tests
* Endoscopy
* Esophagram
* H. Pylori tests
901
What techniques can be used to detect the presence of excessive H. Pylori in order to diagnose peptic ulcers?
* Serology (Blood Test) – Detects elevated antibodies (Immunoglobulin M and G - IgM and IgG) but can’t distinguish past vs. current infection.
* Urea Breath Test – Detects active infection by measuring urease activity.
* Stool Antigen Test – Also detects active infection by looking for proteins (antigens) associated with H. pylori infection in the stool.
* Biopsy (via Endoscopy) – Gold standard for direct detection, but only done if ulcers are suspected.
902
How can a breath test detect the presence of H. pylori infection?
The H. pylori breath test, also called urea breath test, relies on a simple chemical reaction which is based on the natural behaviour of the bacteria.
Naturally occuring gastric urea is made up of 99% carbon isotope 12-C and 1% carbon isotope 13-C. The breath test uses urea enriched with 13-C.
The patient must consume a drink containing 13-C enriched urea and after some time they blow into a tube. If the level of 13-C is elevated, then the enriched urea provided by the testing kit must have been **broken down to produce high levels of 13-C in the breath** (i.e., it means that the 13-C was separated from the urea) and this implies the presence of **urease** excreting H pylori in the stomach (an enzyme produced by this bacteria that degrades urea).
903
What is inflammatory bowel disease?
It is a chronic inflammation of several sections of the gastrointestinal tract, resulting from the immunological action on the intestinal mucosa.
904
How does inflammatory bowel disease differ from other infectious pathologies?
It does not present positive culture results for known microbial/pathological agents (bacteria/virus/fungus) and does not respond to antibiotic treatments.
905
How is the prevalence of inflammatory bowel disease in terms of gender and age?
In terms of gender, it affects men and women equally.
In terms of age, there are two more evident incidence peaks: between 15 and 30 years and between 60 and 80 years.
906
What is the typical presentation of Inflammatory Bowel Disease symptoms?
It often presents with recurrent episodes (with phases of exacerbation and remission) of bloody mucopurulent diarrhea and abdominal pain.
907
What are the two main types of Inflammatory Bowel Disease?
The two main types are Crohn's disease and ulcerative colitis.
908
Distinguish Crohn's disease and ulcerative colitis in terms of affected regions and lesion extension.
Affected regions:
* Crohn's Disease may affect the entire GI tract (from mouth to anus);
* Ulcerative colitis is mainly limited the descending colon, rectum and anus.
Lesion extension:
* Crohn's Disease presents transmural lesions (which affect the entire intestinal wall: mucosa, submucosa, muscularis propria and serosa)
* Ulcerative colitis lesions are usually limited to the mucosa (most superficial/inner layer of the intestinal wall).
909
Which of the two types of inflammatory bowel disease is considered an autoimmune disease?
Crohn's Disease
910
What is the cause of Crohn's disease?
The exact cause of Crohn's disease is idiopathic (still unknown).
911
What factors have been correlated with the etiology of Crohn's Disease?
* **Immune dysregulation**: exacerbated autoimmune inflammatory response.
* **Diet and stress**: can worsen the condition, but it is not certain that they trigger the disease.
* **Genetic factors**: more common in people who have cases in the family and some correlation with the HLA-B27 gene.
912
What are the main risk factors associated with Crohn's Disease?
* Age (< 30 years)
* Smoking habits
* Appendicectomy (the appendix may contribute to intestinal immunity, helping protect the GI tract against infections)
* Stress
* Geographical factors (industrialized countries are associated with higher risk, especially in the northern hemisphere)
913
Describe the pathophysiology of Crohn's Disease.
The exact cause of Crohn's disease is unknown, but it is believed to be triggered by a viral or bacterial infection that initiates an inflammatory response. However, this response does not resolve, leading to persistent inflammation and granulomatous formation. A strong inflammatory response, often linked to hyperactivity of Th-17 lymphocytes, results in thickening and weakening of the gastrointestinal tract walls.
914
What are the main gastrointestinal clinical manifestations of crohn's disease?
* Abdominal pain and cramps
* Chronic diarrhea
* Blood in the stool
* Mouth ulcers
* Loss of appetite and weight
* Pain around the anus
915
What are the main clinical manifestations of crohn's disease outside of the gastrointestinal disease?
* Fatigue
* Fever
* Joint pain/arthritis
* Eye inflammation (e.g. uveitis and episcleritis)
* Osteoporosis
916
What are the main complications of crohn's disease, due to constant aggression to the gastrointestinal walls?
* **Intestinal occlusion**: thickening of the walls and the formation of scar tissue can lead to stenosis in the digestive tract, making it difficult for food to pass through.
* **Ulcers**: small lesions appear on the mucosa of the digestive system (most commonly the mouth, anus and genital region).
* **Fistulas**: when mucosal lesions become deeper, they can connect two parts of the body that are not normally connected (e.g. between the rectum and the skin around the anus).
* **Abscesses**: accumulation of pus.
917
What other complications may arise from crohn's disease?
* Anemia
* Malnutrition
* Skin problems
* Artritis
* Colon cancer
918
What are the main diagnostic methods for crohn's disease and the most common findings in each one?
* **Anamnesis**: family history, abdominal pain and cramps, loss of weight and apetite.
* **Physical examination**: tenderness to abdominal palpation, for example.
* **Endoscopy and/or colonoscopy**: thickening of the walls and the formation of scar tissue can lead to narrowing of the digestive tract.
* **Computed Tomography (CT) or Magnetic Resonance Imaging (MRI)**: MRI is relevant for detecting fistulas and CT helps examine bowel wall.
* **Biochemical analysis of blood and/or feces**: includes complete blood count and inflammation panel (e.g. inflammatory markers – C-reactive protein, ESR, etc.). Additionally, microbial culture tests may be relevant to exclude infectious pathologies.
* **Biopsy**: the presence of clusters of inflammatory cells, called granulomas, will help to confirm a diagnosis of Crohn's disease.
919
A positive microbial culture helps to ________ (confirm/rule out) crohn's disease.
rule out
## Footnote
Crohn's disease is a result of an autoimmune inflammatory response, not derived from a pathogen.
920
Finding granulomas in a colon biopsy helps to ________ (confirm/rule out) crohn's disease.
confirm
## Footnote
It also allows to differentiate Crohn's disease from ulcerative colitis, as the latter does not present granulomas.
921
What is the cause of ulcerative colitis?
The exact cause of ulcerative colitis is idiopathic (still unknown).
922
What factors have been correlated with the etiology of Ulcerative colitis?
* Immune dysregulation (exarcebated autoimmune inflammatory response)
* Diet and stress
* Genetic factors (HLA-B27 gene)
923
T/F: The etiology and risk factors of crohn's disease and ulcerative colitis are all the same.
True
924
Explain the pathophysiology of ulcerative colitis.
Even though the exact cause is unknown, it is believed that it may be triggered by a viral or bacterial infection that leads to an inflammatory response. Typically, this inflammation begins in the anorectal area and extends proximally. Therefore, inflammation is generally limited to the mucosa, and foci of ulceration and abscesses may be seen.
925
What are the main signs and symptoms (clinical manifestations) of ulcerative colitis?
* Abdominal pain and cramps
* Diarrhea with blood, pus and/or mucus
* Urgency to defecate, but unable to do so
* Pain when defecating
* Loss of appetite and weight
926
What symptoms outside the gastrointestinal system are usually observed in ulcerative colitis?
* Fatigue
* Fever
* Joint pain/arthritis
* Eye inflammation (e.g. uveitis and episcleritis).
927
What specific symptoms of ulcerative colitis help to distinguish it from crohn's disease?
* Fecal urgency
* A feeling that the bowels haven't emptied completely
* Significative blood in stool
928
What are the main complications of ulcerative colitis?
* Severe bleeding
* Sudden perforation of the colon (fulminant or toxic colitis): may lead to fistulas and/or peritonitis.
* Osteoporosis
* Lithiasis (kidney stones)
* Colon cancer
929
What other complications may arise from ulcerative colitis?
Same as Crohn's Disease:
* Malnutrition
* Anemia
* Skin problems
* Artritis
* Colon cancer
930
What are the main diagnostic methods for ulcerative colitis and the most common findings in each one?
* **Anamnesis**: abdominal pain and cramps, diarrhea, urgency to defecate.
* **Physical examination**: tenderness to abdominal palpation, for example.
* **Endoscopy and/or colonoscopy**
* **Computed Tomography (CT) or Magnetic Resonance Imaging (MRI)**: MRI is relevant for detecting fistulas and CT helps examine bowel wall.
* **Biochemical analysis of blood and/or feces**: includes complete blood count and inflammation panel (e.g. inflammatory markers – C-reactive protein, ESR, etc.). Additionally, microbial culture tests may be relevant to exclude infectious pathologies.
* **Biopsy**: the presence of clusters of inflammatory cells, called granulomas, will help to confirm a diagnosis of Crohn's disease and rule out ulcerative colitis.
931
How can diagnostic techniques help to differentiate crohn's disease and ulcerative colitis?
In ulcerative colitis, fistulas are usually absent, as well as granulomas, and lesions are limited to the mucosa of the colon, normally presenting with bleeding.
In Crohn's disease, fistulas are common, as well as granulomas, and lesions are transmural (i.e., affect all layers of the walls) can affect the whole GI tract (i.e., from the mouth to the anus), usually without bleeding.
932
What is the irritable bowel syndrome (IBS)?
Hypersentivity of the intestinal muscle tissue to stimuli (triggers) that affects the frequency of bowel movements, as well as the consistency and/or shape of stool.
933
What is the prevalence of IBS in terms of age and gender?
In terms of gender, it affects more women than men.
In terms of age, it is most often diagnosed in young adulthood.
934
What is the etiology (cause) of IBS?
The exact cause of irritable bowel syndrome is idiopathic (still unknown).
935
What factors have been associated with the etiology of IBS?
* **Eating habits**: eating meals too quickly, high-calorie meals, foods rich in wheat, dairy, chocolate, coffee, spicy foods, etc.
* **Somatic pain syndromes** (pain in the musculoskeletal structures or skin): fibromyalgia, chronic fatigue, functional heart pain, etc.
* **Emotional and/or psychiatric disorders**: depressive disorders, anxiety, stress, fear, etc.
* **Other gastrointestinal disorders**: bacterial gastroenteritis, etc.
936
Describe the possible pathophysiology of IBS.
**Changes in the sensitivity of nerve pathways, both intrinsic and extrinsic to the intestine** (including neuron necrosis), can lead to exaggerated sensations of pain (hyperalgesia) and/or alterations in secretion, absorption, and intestinal motility, such as **decreased peristalsis**. This slowed motility can cause feces to be retained longer, potentially leading to **intestinal dysbiosis**, which is an imbalance in the intestinal microbiota. Dysbiosis may alter the permeability of the mucus layer, allowing pathogens to invade the intestinal lining, potentially causing inflammation and impairing normal nutrient absorption
937
What are the main clinical manifestations of IBS?
* Diarrhea alternating with constipation
* Changes in intestinal transit
* Presence of mucus in the stool
* Abdominal pain
* Abdominal distension (due to excess gas)
* Flatulence
* Nausea, reflux and early satiety
938
What are the main complications of IBS?
* **Malnutrition and dehydration**: result of possible electrolyte dysregulation caused by diarrhea or by dietary habits that involve avoiding certain essential foods (by triggering flareups).
* **Anxiety disorders and depression**: symptom and crisis management can generate additional anxiety.
* **Hemorrhoids**: in the case of recurrent constipation.
* **Sleep perturbations**: abdominal discomfort and pain, associated with changes in intestinal transit, can affect the quality of sleep.
* **Impact on quality of life**: management of the urge to defecate and management of pain/discomfort in a social environment.
939
What are the main diagnostic methods for IBS and the most common findings in each one?
* **Physical examination and anamnesis**: may show tenderness in the abdomen, especially in the lower abdomen, and signs of bloating or discomfort. The patient may appear thin and pale. There might be complaints of the urgency to defecate.
* **Biochemical analyses of blood and/or feces**: typically normal, with no signs of infection or inflammation, and may show mild anemia or altered electrolyte levels in some cases.
* **Endoscopy and/or colonoscopy**: usually normal, with no visible damage or inflammation in the intestinal lining.
* **Computed tomography (CT) or Magnetic Resonance Imaging (MRI)**: typically show no structural abnormalities, but may reveal signs of bloating or gas accumulation.
* **Psychological evaluation exams**: may indicate anxiety, depression, or stress-related factors that can exacerbate IBS symptoms.
940
What is diverticular disease?
It is characterized by the presence of dilations in the mucosa that form a type of balloon-shaped sac, the diverticula.
941
Distinguish diverticulosis and diverticulitis.
The presence of diverticula is called diverticulosis. When inflammation of the diverticula occurs, it is a condition called diverticulitis.
942
What are the main risk factors of diverticular disease?
* Sedentary lifestyle
* Smoking habits
* Eating habits (high-calorie meals, meals rich in wheat, dairy products, chocolate, coffee, spicy foods, etc)
943
What is the probable cause of diverticulosis?
The exact cause of diverticulosis is still uncertain (idiopathic). However, it may be linked to **muscle layer spasms**. Some studies indicate that the origin of diverticula may be related to spasms in the muscular layer of the intestine, since the inner layer of the wall is pushed through weak spots in the muscular wall, leading to the formation of diverticula.
944
What is the probable cause of diverticulitis?
The causes behind diverticulitis are still unknown, but it is thought that it may be related to **mechanical forces**, such as increased pressure in the colon or the closing of the diverticulum opening by feces, which can lead to its infection and inflammation. Diverticulitis is also considered in light of the **existence of small holes in the wall of the diverticulum** that allow the entry of microbial agents that trigger an inflammatory process.
945
What are the clinical manifestations of diverticulosis?
Diverticulosis is usually **asymptomatic** but is sometimes associated with:
* abdominal discomfort/pain (in the lower left quadrant) that is relieved by defecation
* diarrhea
* cramping
* changes in bowel habits
* occasionally rectal bleeding
946
What are the clinical manifestations of diverticulitis?
* Abdominal pain/tenderness
* Fever and chills
* Change in bowel habits
* Nausea and vomiting
947
What are the main complications of diverticular disease?
* Bowel obstruction
* Intestinal stenosis and necrosis
* Fistulas
* Abscesses
* Peritonitis
* Inflammation of adjacent organs
* Intestinal bleeding
948
What are the main diagnostic methods for diverticular disease and what are the most common findings in each one?
* **Physical examination and anamnesis**: atients may present with left lower quadrant abdominal pain, tenderness, bloating, and possible signs of mild fever in diverticulitis.
* **Biochemical blood tests**: may show elevated white blood cell count (leukocytosis) and increased C-reactive protein (CRP) in cases of inflammation or infection (diverticulitis), but are usually normal in diverticulosis.
* **Colonoscopy**: visible diverticula (small pouches in the intestinal wall), but colonoscopy is generally avoided during acute diverticulitis due to the risk of perforation.
* **Computed tomography (CT) or Magnetic Resonance Imaging (MRI)**: CT scan is the gold standard in acute cases, showing inflamed or thickened bowel walls, diverticula, abscesses, or signs of perforation. MRI can also detect inflammation but is used less frequently.
949
What are the main types of acute renal failure?
* **Pre-renal**: Reduced blood flow to the kidneys.
* **Renal** (intrinsic): Direct damage to the renal parenchyma.
* **Post-renal**: Obstruction of urinary flow.
950
What arteries enter the kidneys through the hilum?
The **renal arteries** branch off from the aorta to supply oxygenated blood to the kidneys. The right renal artery supplies blood to the right kidney, and the left renal artery supplies blood to the left kidney.
951
How is the kidney structurally divided internally?
Internally, the kidney is divided into the renal cortex (outer layer), renal medulla (inner layer), renal pyramids, renal columns, calyces (minor and major), and renal pelvis.
952
What is the function of the renal cortex and medulla?
The renal cortex contains glomeruli and is where filtration begins, while the renal medulla contains renal pyramids that help concentrate urine and transport it to the calyces.
953
What is the renal pelvis and what does it do?
The renal pelvis is a funnel-shaped structure that collects urine from the major calyces and passes it into the ureter for transport to the bladder.
954
What structures are involved in the flow of urine from the nephron to the ureter?
Urine flows from the nephron → renal papilla → minor calyx → major calyx → renal pelvis → ureter
955
What are renal pyramids and where are they located?
Renal pyramids are cone-shaped structures found in the medulla. They contain tubules (i.e., the loops of Henle and collecting ducts), which allow to concentrate and transport urine to the renal papillae.
956
Match the part of the nephron to its function.
Parts:
A. Glomerulus
B. Proximal Convoluted Tubule
C. Loop of Henle
D. Distal Convoluted Tubule
E. Collecting Duct
Functions:
a. Filtration of blood, allowing water and small molecules to pass through.
b. Selective reabsorption of water, sodium, and other ions.
c. Reabsorption of water, concentrating urine.
d. Further modification of filtrate, including secretion of waste.
e. Collection and final adjustment of urine concentration before excretion.
* A) a
* B) b
* C) c
* D) d
* E) e
957
A patient presents with a kidney disease that affects the filtration barrier of the glomerulus. What would likely be the result of this condition?
A. Increased filtration of proteins into the urine
B. Decreased secretion of waste products
C. Increased water reabsorption
D. Decreased production of urine
**A. Increased filtration of proteins into the urine**
When the glomerular filtration barrier is damaged, it may allow proteins like albumin to leak into the urine, a condition called proteinuria.
958
What are the main renal functions?
* Excretion of metabolites (urea, ammonia, uric acid, organic acids/bases) through blood filtration
* Hydro-electrolyte balance (change in urine composition)
* Acid-base (pH) balance (change in urine composition)
* Regulation of blood pressure (through increase or decrease in volemia)
* Endocrine secretion (erythropoietin, vitamin D, renin)
959
What is the main function of the renal corpuscle?
| (part of the nephrons)
Generate the glomerular filtrate, composed by water, ions, and small molecules
960
What is the main function of the proximal convoluted tubule?
| (part of the nephrons)
It reabsorbs sodium chloride, potassium, water, glucose, amino acids, bicarbonate, calcium and phosphate, and secretes amonium and creatinine.
961
What is the main function of thin descending limb of the loop of Henle?
| (part of the nephrons)
Water reabsorption
962
What is the main function of thin ascending limb of the loop of Henle?
| (part of the nephrons)
Sodium and chloride reabsorption
963
What is the main function of thick ascending limb of the loop of Henle?
| (part of the nephrons)
Amonium, sodium and chloride reabsorption
964
What is the main function of the distal convoluted tube?
| (part of the nephrons)
Sodium and chloride reabsorption
965
What is the main function of collecting duct?
| (part of the nephrons)
Reabsorbs sodium, chloride and water, and secretes amonium, hydrogen ions and potassium
966
Glomerular filtration rate (GFR) reflects the ________ of functional nephrons
quantity
967
Explain the RAA system in blood pressure regulation.
When there is a low perfusion pressure in the kidneys (indicading low arterial blood pressure), they produce renin, which converts the angiotensinogen (produced by the liver and circulating in the blood stream) into angiotensin I. Then, in the lungs, the angiotensin converting enzyme (ACE) converts angiotension I into angiotensin II, which promotes arteriolar vasoconstriction, as well as the secretion of ADH (antidiuretic hormone) by the pituary gland and aldosterone (mineralocorticoid steroid hormone) by the adrenal glands that increase water reabsorption in the kidney, in order to increase blood volemia and, consequently, increase blood pressure.
968
Indicate and explain each of the 4 hydrostatic and osmotic pressures that influence glomerular filtration.
* **Hydrostatic Pressure in the Glomerular Capillaries (Pc)**: the pressure exerted by blood inside the glomerular capillaries is the main force pushing fluid out of the capillaries and into the Bowman’s capsule.
* **Hydrostatic Pressure in the Bowman’s Space (Pb)**: this is the pressure exerted by the filtrate already inside the Bowman’s capsule.
* **Osmotic Pressure in the Glomerular Capillaries (πc)**: this pressure is created by the proteins (mainly albumin) that remain in the blood. These proteins draw water back into the glomerular capillaries.
* **Osmotic Pressure in the Bowman’s Space (πb)**: this is usually negligible, as proteins are not typically found in the Bowman’s space.
969
The glomerular filtration rate (GFR) is the rate at which the kidneys filter blood, and it is influenced by the balance of the ____________ and ________ pressures, as well as by the ________ in the afferent and efferent arterioles.
hydrostatic, osmotic, resistance
970
What happens to the glomerular filtration rate (GFR) when there is a vasoconstriction of the afferent arteriole in the glomerulus?
Constriction of the afferent arteriole reduces blood flow into the glomerulus, decreasing the hydrostatic pressure in the glomerular capillaries (Pc) and thus reducing the GFR.
971
What happens to the glomerular filtration rate (GFR) when there is a vasoconstriction of the efferent arteriole in the glomerulus?
Constriction of the efferent arteriole increases hydrostatic pressure within the glomerulus (hydrostatic pressure in the glomerular capillaries, Pc), which can increase the GFR, while dilation of the efferent arteriole decreases GFR.
972
A patient with hypertension is prescribed a medication that causes constriction of the afferent arteriole. What would be the effect on their glomerular filtration rate (GFR)?
A. Increase GFR
B. Decrease GFR
C. No change in GFR
D. Increase osmotic pressure in Bowman’s space
**B. Decrease GFR**
Constriction of the afferent arteriole reduces blood flow into the glomerulus, lowering the hydrostatic pressure and reducing the GFR.
973
What is the effect of an increase in osmotic pressure in the glomerular capillaries (πGC) on the glomerular filtration rate (GFR)?
A. Increase GFR
B. Decrease GFR
C. No change in GFR
D. It is irrelevant to GFR
**B. Decrease GFR**
An increase in osmotic pressure in the glomerular capillaries would attract more water into the capillaries, reducing the amount of filtrate formed and thus decreasing the GFR.
974
Why does glomerular filtration rate (GFR) increase with resistance in the efferent arteriole up to a certain point, then decrease despite further resistance?
Initially, increased resistance in the efferent arteriole raises glomerular hydrostatic pressure (because the blood cannot leave as easily), promoting filtration (as it pushes fluid out of the capillaries and into the Bowman’s capsule) and, thus, increasing GFR.
However, at high resistance, the body compensates by raising the pressure to maintain filtration, leading to higher resistance in the afferent arteriole. This leads to a decrease in blood flow entering the glomerulus, reducing perfusion and eventually decreasing GFR.
975
What physiological parameters can be measured to evaluate kidney function?
* Glomerular Filtration Rate
* Urea-Creatinine Ratio
* Urinary Osmolarity
* Fraction of sodium excreted in the urine
976
What imaging techniques can be used to assess kidney function?
* Ultrasound
* Computerised tomography (CT)
* Magnetic Resonance Imaging (MRI)
* Radiography
977
How can we estimate the glomerular filtration rate?
We can't measure GFR directly, but we can estimate it through the **Creatinine clearance method** and/or applying **estimation equations**.
1. Creatinine is a byproduct of muscle metabolism and is filtered freely by the glomerulus. It is neither reabsorbed nor significantly secreted, making it a reliable marker for kidney function. **Creatinine clearance is an estimate of GFR because it reflects the volume of plasma cleared of creatinine per minute**. It can be calculated by measuring the concentration of creatinine in urine and blood.
2. Based on serum creatinine, we can also apply the following equations:
* **Cockcroft-Gault Equation**: estimates kidney function based on age, weight, and serum creatinine levels, but it may overestimate GFR in patients with normal kidney function.
* **MDRD (Modification of Diet in Renal Disease) Equation**: widely used in clinical settings and adjusts for race and sex, but tends to underestimate GFR in patients with higher GFR.
* **CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration)**: this equation is considered more accurate than MDRD, especially in those with normal or mildly reduced GFR. It uses age, sex, race, and serum creatinine levels to estimate GFR.
978
What is the normal Urea-Creatinine Ratio?
40-110:1
979
The accumulation of nitrogen products (urea and creatinine) in the blood is called ________ and reflects a ________ (high/low) glomerular filtration rate.
azotemia, low
980
How can azotemia be classified according to the origin of the renal lesion? What are the urea-creatinine ratio values associated with each type?
* Pre-renal (U/Cr > 110:1)
* Intra-renal (U/Cr < 40:1, but U and Cr are both elevated)
* Post-renal (normal U/Cr, of 40:110:1)
981
What are the main parameters to analyze in urine?
Appearance, color, density, and composition, concentration and volume.
982
What is the normal osmolarity (concentration of solute) range for urine?
500-850 mOsm/kg
983
The normal range for osmolarity of urine is 500-850 mOsm/kg. When osmolarity of urine is < 350 mOsm/kg, it indicates ________ (pre-renal dysfunction/intra-renal dysfunction).
intra-renal dysfunction
984
What is the normal urine volume per day?
400 to 2500 mL/day, depending on fluid intake
985
What is polyuria?
Polyuria refers to a high urine output, with a volume of urine usually > 2500 mL/day.
986
What is oliguria?
Oliguria refers to a low urine output, with a volume of urine usually < 400 mL/day.
987
What is anuria?
Anuria is nonpassage of urine, with an urine volume < 100 mL/day or absence of urination.
988
What is pollakiuria?
Increased frequency of urination
989
What is nocturia?
The urge to urinate during the night.
990
What is dysuria?
Pain or difficulty when urinating.
991
Renal failure is characterized by an ________ (increased/normal/decreased) glomerular filtration rate.
decreased
992
What are the two main types of renal failure?
Acute kidney injury (AKI) and chronic kidney disease (CKD).
993
What is acute kidney injury (AKI)?
A rapid decline in kidney function over hours to days, often reversible if treated promptly.
994
What is chronic kidney disease (CKD)?
A progressive and irreversible loss of kidney function over months to years.
995
What percentage of acute kidney injury cases are due to pre-renal causes?
About 60%
996
What percentage of acute kidney injury cases are due to intra-renal causes?
About 35%
997
What percentage of acute kidney injury cases are due to post-renal causes?
About 5%
998
What are the three main causes of renal failure?
* Pre-renal causes: reduction in kidney perfusion.
* Intra-renal causes: damage to the kidney tissues.
* Post-renal causes: obstruction of urine flow.
999
What is renal failure?
Renal failure is the inability of the kidneys to adequately filter waste products and maintain fluid, electrolyte, and acid-base balance, i.e., to maintain their normal functions.
1000
Pre-renal failure occurs when there is a reduction in ________ in the kidneys and/or ________ (low/high) glomerular filtration rate.
perfusion, low
1001
Intra-renal failure involves direct ________ to kidney tissues.
damage
1002
Post-renal failure is caused by ________ of urine flow.
obstruction
1003
What is the main mechanism behind pre-renal failure?
The central mechanism is a reduction in the distribution of blood to the kidney, which compromises renal filtration capacity.
1004
How does heart failure lead to pre-renal failure?
Reduced cardiac output decreases blood volume and blood pressure, including in the renal artery, which decreases renal perfusion.
1005
How does renal artery stenosis affect GFR and cause pre-renal failure?
Narrowing of the renal artery reduces blood flow, lowering glomerular filtration pressure and, thus, GFR, leading to pre-renal failure.
1006
How does sepsis cause pre-renal failure?
Systemic vasodilation (due to inflammatory response) and consequent hypotension reduce renal artery pressure and renal perfusion.
1007
How do hemorrhage, vomiting, or diarrhea contribute to pre-renal failure?
They cause hypovolemia, lowering blood pressure and renal perfusion.
1008
How does dehydration contribute to pre-renal failure?
Dehydration causes a decreased blood volume, which reduces renal artery blood flow and pressure, decreasing renal perfusion and GFR.
1009
How do NSAIDs contribute to pre-renal failure?
NSAIDs inhibit prostaglandin synthesis (D2 and E2) - hormone-like substances that promote inflammation - reducing afferent arteriole vasodilation, which lowers glomerular capillary pressure and GFR.
1010
How do Angiotensin-converting enzyme (ACE) inhibitors cause pre-renal failure?
ACE is the enzyme responsible for converting angiotensin I in angiotensin II, which induces arteriole vasoconstriction. Therefore, ACE inhibitors reduce angiotensin II, which normally constricts the efferent arteriole. Less constriction (aka less resistance) leads to decreased glomerular pressure (since blood can flow out without resistance) and GFR.
1011
How does hypercalcemia contribute to pre-renal failure?
Hypercalcemia can result when too much calcium enters the extracellular fluid (e.g., blood) or when there is insufficient calcium excretion from the kidneys.
Calcium induces smooth muscle contraction and, therefore, causes induces afferent arteriole vasoconstriction. This reduces blood flow to the glomerulus, reducing glomerular capillary pressure, reducing hydrostatic pressure and, thus, reducing GFR.
Calcium also reduces reabsorption of sodium, chloride, and water in the Henle loop, so more fluid stays in the urine, and less is retained in the body, leading to fluid loss which contributes to hypovolemia, reducing renal artery pressure and renal perfusion.
1012
T/F: NSAIDs reduce GFR by increasing afferent arteriole vasodilation.
False. NSAIDs decrease vasodilation, leading to vasoconstriction and lower GFR.
1013
T/F: ACE inhibitors decrease efferent arteriole resistance.
True. They inhibit angiotensin II, causing vasodilation of the efferent arteriole.
1014
NSAIDs inhibit ________, leading to reduced afferent arteriole vasodilation.
prostaglandins (D2 and E2)
1015
ACE inhibitors reduce levels of ________, causing dilation of the efferent arteriole.
angiotensin II
1016
Hypovolemia leads to decreased ________, resulting in lower GFR.
renal artery pressure
1017
A 75-year-old male presents with hypotension and recent vomiting. Labs show increased serum creatinine.
**What is the likely cause of his acute renal failure?**
Pre-renal failure due to hypovolemia from fluid loss (vomiting) and hypotension, leading to decreased renal perfusion.
* Vomiting → fluid loss → ↓ intravascular volume → hypotension → ↓ renal perfusion pressure → ↓ glomerular filtration → ↑ serum creatinine
1018
What are the two main causes of intra-renal failure?
* Glomerulopathies
* Tubulointerstitial diseases
1019
What are the 4 main manifestations of glomerulopathies?
* Hematuria (blood in urine)
* Proteinuria (proteins in urine)
* Decreased glomerular filtration rate
* Hypertension
1020
What are the two main types of glomerulopathies?
* Nephrotic syndrome
* Nephritic syndrome
1021
What is nephrotic syndrome?
It's a condition that causes the deposition of proteins in unknown autoimmune context or context that damage the filtration membrane.
1022
What is nephritic syndrome?
Damaging inflammatory response to a bacterial or viral infection that damages the filtration membrane.
1023
What are the main bacterial and viral infections that lead to nephritic syndrome?
Bacterial infections:
* Pharyngitis
* Streptococcal tonsillitis
* Bacterial endocarditis
* Infectious cellulitis
Viral infections:
* Hepatitis B and C
1024
Why does nephritic syndrome decrease the glomerular filtration rate?
Because inflammation of the glomeruli leads to cell proliferation, leukocyte infiltration, and thickening of the glomerular basement membrane, which narrow or block capillary lumens, reducing the surface area available for filtration and decreasing GFR.
1025
Why does a decreased glomerular filtration rate in nephritic syndrome cause hypertension, edema and oliguria?
↓ GFR causes fluid and sodium retention, activating the RAAS (the kidney responds to low GFR as if it were hypoperfused) and increasing blood volume and systemic vascular resistance. This leads to hypertension, edema from fluid and sodium retention, and oliguria due to reduced urine output from decreased filtration.
1026
In nephritic syndrome, an inflammatory process triggers the release of ________ which induce glomerular damage.
cytokines
1027
Why does nephritic syndrome lead to hematuria and proteinuria?
Glomerular inflammation damages the glomerular capillary walls, increasing their permeability. This allows red blood cells and proteins (mainly albumin) to pass into the urine, leading to hematuria and mild to moderate proteinuria.
1028
Why does nephritic syndrome lead to azotemia?
Azotemia is a biochemical abnormality, defined as elevation, or buildup of, nitrogenous products.
Nephritic syndrome can lead to azotemia because inflammation decreases the glomerular filtration rate (GFR), reducing the kidneys’ ability to excrete nitrogenous waste products like urea and creatinine, which then accumulate in the blood.
1029
What type of edema is usually seen in nephritic syndrome?
Positive Godet edema, namely periorbital (swollen eyelids) and peripheral (swelling in the arms or legs).
1030
What are the main primary causes of nephrotic syndrome?
* Minimal change disease
* Focal segmental glomerulosclerosis
* Membranous nephropathy
* Glomeruloproliferative glomerulonephritis
1031
What are the main secondary causes of nephrotic syndrome?
* Diabetic nephropathy
* Amyloid nephropathy (deposition of proteins with an abnormal conformation)
* Lupus nephritis
1032
How does nephrotic syndrome cause hypoproteinemia and hypoalbuminemia?
Damage to the glomerular filtration barrier increases its permeability, allowing large amounts of plasma proteins—especially albumin—to be lost in the urine. This leads to hypoproteinemia and specifically hypoalbuminemia in the blood.
1033
How does nephrotic syndrome lead to lipiduria?
In nephrotic syndrome, hypoalbuminemia due to proteinuria stimulates the liver to increase lipoprotein (VLDL) synthesis, causing hyperlipidemia. Some of these excess lipids spill into the urine, leading to lipiduria, often visible as fatty casts or “oval fat bodies” in the urine.
1034
Why does nephrotic syndrome cause edema?
Nephrotic syndrome causes hypoalbuminemia, which lowers plasma oncotic pressure (pressure created by proteins in the blood). This causes fluid to shift from the blood vessels into the interstitial tissues, leading to edema.
1035
How does the loss of different proteins in nephrotic syndrome contribute to its complications? Refer to antibodies, antithrombin III, vitamin-D binding proteins and thyroxine-binding globulin.
The loss of various proteins in nephrotic syndrome has specific consequences:
* Antibodies → ↑ susceptibility to infections
* Antithrombin III → ↑ hypercoagulability (risk of thrombosis)
* Vitamin D-binding proteins → Vitamin D deficiency (bone health issues)
* Thyroxine-binding globulin → Thyroid dysfunction (altered thyroid hormone levels)
1036
What are the main clinical manifestations of nephrotic syndrome?
* Edema
* Foamy urine
* Hypertension
* Symptoms of hypocalcemia (tetany, paresthesia, spasms)
* Muehrcke lines in fingernails (multiple transverse white linear bands parallel to the lunula of the fingernail)
1037
What are tubulointerstitial diseases?
Tubulointerstitial diseases are kidney diseases that affect the kidney's tubules and interstitium (including the connective tissue and medullary vasculature).
1038
What causes tubulointerstitial diseases?
1) **Bacterial infection** that reaches the kidney through:
* the bloodstream (less common)
* asceding dissemination (i.e., starts at the periurethral area and goes up through the urethra, bladder, ureter and reaches the kidneys) - **urinary tract infection** (UTI).
2) **Drugs** (penicillins, sulphonamides, NSAIDs) that lead to hypersensibility reactions or nephrotoxic lesion.
1039
Why are women more susceptible than men to UTIs?
* Vaginal bacterial ‘reservoir’ (fecal origin) due to closer proximity to the anus;
* Shorter urethra;
* Absence of antibacterial secretions (men have the prostatic fluid).
1040
What are the four main factors that determine the progression of a UTI?
* Genetic susceptibility to bacterial adhesion;
* Bacterial species;
* Vesicoureteral reflux (backward flow of urine from the bladder into the ureters and sometimes the kidneys);
* Uretero-renal reflux (backward flow of urine from the ureters into the renal pelvis and kidneys).
1041
If an UTI reaches the kidneys, it is called ________.
pyelonephritis
1042
How can we differentiate a lower UTI (restricted to the urethra and bladder) from pyelonephritis (kidney infection) based on symptoms?
* Lower UTI: Local urinary symptoms (dysuria, urgency, frequency), no systemic signs (no fever or flank pain).
* Pyelonephritis: Includes systemic signs (fever, chills, flank pain) and signs of kidney involvement like cellular casts.
1043
If acute pyelonephritis is not resolved, what are the possible pathological consequences in the kidney?
* **Neutrophil infiltration** into the renal interstitium and tubules (neutrophils release proteolytic enzymes and reactive oxygen species to kill pathogens, but these molecules also damage nearby renal tissue);
* **Replacement by granulation tissue** (connective tissue) during the healing phase;
* **Possible abscess formation** if necrosis and pus accumulate;
* **Fibrosis and scar tissue formation**, potentially leading to chronic kidney dysfunction.
1044
What are two major causes of acute tubular necrosis?
* Ischemia (e.g. prolonged hypotension or hypoperfusion)
* Toxins from hemolysis (free hemoglobin) or rhabdomyolysis (myoglobin release)
Both cause direct tubular cell injury, leading to necrosis and loss of function.
1045
What are key vascular conditions that can lead to intrinsic renal failure?
* **Hypertensive crisis** → damages small renal vessels
* **Renal vein thrombosis** → obstructs venous outflow and increases pressure
* **Vasculitis** → immune-mediated inflammation of renal vessels
1046
How do vascular diseases impair kidney function?
They reduce perfusion, cause inflammation, and/or lead to vascular obstruction, which can result in ischemia and glomerular damage.
1047
How can acute tubular necrosis evolve into tubulointerstitial disease?
Persistent or severe ATN can cause chronic inflammation and fibrosis of the interstitium, leading to tubulointerstitial disease with progressive loss of renal function.
1048
What are the main post-renal causes of renal failure?
Intra- (collecting ducts, pelvis) or extra-renal (ureter,bladder) obstructions which, in the absence of resolution, lead to irreversible damage
with renal atrophy. Namely:
* Renal lithiasis (kidney stones)
* Neurogenic bladder
* Benign prostatic hyperplasia
1049
What are some of the conditions that cause acquired obstruction in the kidneys, ultimately leading to post-renal failure?
* Benign prostatic hyperplasia
* Neoplasms (e.g., bladder, cervix or metastases)
* Intrarenal obstruction after acute tubular necrosis event
* Single kidney lithiasis (kidney stones)
* Neurogenic bladder (condition that causes loss of bladder control due to nerve damage in the brain, spinal cord, or nerves)
* Iatrogenic (ladder injury that occurs as a result of medical care, such as surgery)
1050
What is Myeloma Kidney (a.k.a. "Myeloma Cast Nephropathy")?
“Myeloma kidney” is renal impairment caused by multiple myeloma (blood cancer that develops in plasma cells in the bone marrow) or similar plasma cell dyscrasias (e.g., AL amyloidosis). It leads to intrarenal obstruction from light chain casts and tubular toxicity.
1051
What are the main lifestyle risk factors for the development of renal lithiasis (kidney stones)?
* High intake of animal protein
* High sodium consumption
* Low intake of chelating agents, such as: citrate, dietary fiber and alkaline foods (e.g. fruits and vegetables)
* Low water intake
1052
What metabolic diseases are associated with renal lithiasis?
* Hypercalciuria (excess calcium in urine);
* Hyperuricosuria (excess uric acid in urine);
* Hyperoxaluria (excess oxalate in urine);
* Hypocitraturia (low levels of citrate in urine);
* Gout (inflammatory arthritis), due to high uric acid levels.
1053
Why does low water intake increase the risk of kidney stones?
Reduced fluid intake lowers urine volume, increasing urine concentration and promoting crystal formation.
1054
How does hyperparathyroidism contribute to renal lithiasis?
Hyperparathyroidism causes hypercalcemia and hypercalciuria, promoting the formation of calcium-based kidney stones (especially calcium oxalate or phosphate).
1055
Why do recurrent urinary tract infections increase the risk of kidney stones?
Certain bacteria produce urease, which raises urinary pH and promotes the formation of struvite stones (magnesium ammonium phosphate).
1056
Is kidney stone formation influenced by genetics?
Yes — family history increases the risk of stone formation due to inherited metabolic or structural factors affecting urine composition.
1057
How does inflammatory bowel disease (IBD) increase the risk of renal lithiasi?
In inflammatory bowel disease (especially Crohn’s disease), fat malabsorption leads to increased oxalate absorption in the gut, causing hyperoxaluria and leading to the formation of calcium oxalate stones.
1058
What’s the link between obesity, hypertension, and kidney stones?
Both hypertension and obesity are associated with altered calcium and uric acid metabolism, acidic urine, and increased stone risk.
1059
Why is the absence of intestinal oxalate-degrading bacteria a risk factor for kidney stones?
Some bacteria degrade oxalate in the intestine. Without them, more oxalate is absorbed and excreted in urine, increasing risk for calcium oxalate stones.
1060
Which medications increase the risk of kidney stones?
Lithogenic drugs promote crystal formation in the urine. Examples:
* Loop diuretics
* Topiramate
* Indinavir
* Vitamin D in excess
* Calcium supplements
1061
What are the four types of renal lithiasis?
* Calcium (oxalate or phosphate) - 80%
* Struvite (magnesium ammonium phosphate) - 10%
* Uric acid - 3-10%
* Cystine - < 2%
1062
What is the main cause of struvite kidney stones?
Often due to recurrent UTIs caused by urease-positive bacteria (e.g. Proteus mirabilis).
1063
What causes cystine kidney stones?
Caused by cystinuria, a recessive genetic disorder, in which defective proximal reabsorption of cysteine leads to stone formation.
1064
What are the main causes of calcium (oxalate or phosphate) kidney stones?
Metabolic conditions such as hypercalciuria, hyperoxaluria, and hypocitraturia.
1065
Why are struvite stones more common in females?
Because women are more prone to urinary tract infections (shorter urethra and anatomical proximity between the urethra and anus) caused by urease-positive bacteria, which increase urine pH and promote struvite crystal formation.
1066
Why are uric acid stones more common in males?
Men have higher rates of gout and purine-rich diets (animal protein), which lead to acidic urine and increased uric acid levels.
1067
What are the classical clinical manifestations of renal lithiasis?
* Severe flank pain
* Hematuria (macro or microscopic)
* ± Fever (may or may not be present)
1068
What can bilateral lithiasis or a stone in a solitary kidney cause?
* Anuria (no urine output)
* Post-renal azotemia (↑ nitrogenous waste due to obstruction)
1069
Why does hematuria occur in renal lithiasis?
The kidney stones cause mechanical trauma to the urinary tract mucosa, leading to blood in the urine.
1070
What is the gold standard imaging technique for diagnosing kidney stones?
Non-contrast helical **CT scan** (CT KUB)
→ High sensitivity and specificity
→ Can detect all types of stones
→ Fast and does not require contrast
1071
Which imaging technique can be used to detect calcium-based kidney stones, but not for uric-acid stones?
X-ray.
It detects radiopaque stones, such as **calcium-based** stones, but misses radiolucent stones, such as **uric-acid** stones.
1072
What are the three main complications of renal lithiasis?
* Hydronephrosis (accumulation of urine in the kidneys due to obstruction)
* Kidney abscess or infection
* Renal failure
1073
How can kidney stones lead to hydronephrosis?
A stone obstructs urine flow, increasing pressure in the urinary tract and causing dilation of the renal pelvis and calyces (hydronephrosis).
1074
Why can kidney stones cause renal abscess or infection?
Obstructed urine flow provides an ideal environment for bacterial growth, leading to urinary tract infections or renal abscess formation.
1075
In what cases can kidney stones cause renal insufficiency/failure?
If bilateral obstruction or obstruction in a single functioning kidney occurs, it can result in acute or chronic kidney failure due to impaired filtration.
1076
What is neurogenic bladder?
It’s a bladder dysfunction caused by a **disruption in the coordination between the central and peripheral nervous systems**, affecting storage or voiding of urine (aka bladder control).
1077
What are the two main imaging techniques used for the diagnosis of kidney stones?
* CT
* Ecography
1078
Name common etiologies of neurogenic bladder.
* Multiple sclerosis
* Parkinson’s disease
* Stroke (AVC)
* Diabetes mellitus (diabetic neuropathy)
* Cauda equina syndrome
* Paralytic syndromes
* Spinal trauma
1079
How can diabetes mellitus cause neurogenic bladder?
Autonomic neuropathy damages the nerves controlling bladder function, leading to impaired sensation, incomplete emptying, or overflow incontinence.
1080
What are the complications associated with neurogenic bladder?
* Urinary retention
* Recurrent urinary tract infections (UTIs)
* Kidney damage (hydronephrosis, reflux)
* Incontinence
1081
What is Benign Prostatic Hyperplasia?
A non-cancerous enlargement of the prostate that usually begins around age 30 and can compress the urethra, affecting urination.
1082
Name common urinary symptoms of Benign Prostatic Hyperplasia.
* Urinary incontinence
* Increased urinary frequency (pollakiuria)
* Nocturia (nighttime urination)
* Dysuria (painful urination)
1083
What complications can arise from untreated Benign Prostatic Hyperplasia?
* Urinary tract infections (UTIs)
* Kidney stones (renal lithiasis)
* Urinary retention
* Acute renal failure
1084
How can Benign Prostatic Hyperplasia lead to acute renal failure?
Prostatic enlargement can block urine outflow, leading to urinary retention, increased pressure in the urinary tract, and eventually reduced glomerular filtration.
1085
What are the four phases of acute renal failure?
* Initiation Phase
* Maintenance Phase
* Diuretic (Polyuric) Phase
* Recovery Phase
1086
What are the manifestations of the initiation phase of acute renal failure?
The patient may feel fatigue and discomfort, as well as symptoms of an underlying cause, but **renal function still appear normal**.
1087
What characterizes the maintenance phase of acute renal failure?
* Oliguria (low urine output) or anuria (no urine output) lasting 1–3 weeks
* Azotemia (↑ urea and creatinine)
* Fluid retention → peripheral edema, dyspnea, orthopnea, crackles, S3
* Metabolic changes: hyperkalemia, acidosis, uremia → lethargy, asterixis (tremors)
1088
What are the signs of the diuretic phase of acute renal failure?
There's an increase in the urine output, up to 3 to 5 L per day, which leads to electrolyte losses (hypokalemia, hyponatremia, hypocalcemia, hypomagnesemia).
1089
What defines Chronic Kidney Disease (or chronic renal failure)?
Defined by a decrease in glomerular filtration rate (GFR) or persistent albuminuria for more than 3 months.
1090
What structural kidney changes are seen in chronic renal failure?
* Bilateral renal atrophy (reduced kidney size)
* Interstitial fibrosis
* Glomerular scarring
1091
How many stages of chronic renal failure are there and what are they based on?
There are 5 stages, based on GFR levels.
1092
What is chronic renal failure Stage 1?
* Normal or elevated GFR > 90 mL/min
* Usually with evidence of kidney damage (e.g., albuminuria)
1093
What is chronic renal failure Stage 2?
* GFR = 60–89 mL/min
* **Mild** decrease in kidney function
1094
What is chronic renal failure Stage 3A?
* GFR = 45–59 mL/min
* **Moderate** decrease in kidney function
1095
What is chronic renal failure Stage 3B?
* GFR = 30–44 mL/min
* **Moderate** to severe reduction in kidney function
1096
What is chronic renal failure Stage 4?
* GFR = 15–29 mL/min
* Severe decrease in kidney function
* Often symptomatic
1097
What is chronic renal failure Stage 5?
* GFR < 15 mL/min
* End-stage chronic renal failure
* Requires dialysis or kidney transplant
1098
What are the six main causes of chronic renal failure?
* Diabetes mellitus (diabetic nephropathy)
* Hypertension
* Recurrent UTIs
* Glomerulopathies
* Chronic nephrolithiasis (kidney stones)
* Polycystic kidney disease
1099
Why do chronic renal failure patients appear pale and fatigued?
Chronic renal failure **impairs the production of erythropoietin** by the kidneys, decreasing erythropoiesis (production of red blood cells). Therefore, the portion of red blood cells in the blood decreases (low hematocrit), leading to **anemia**, which causes fatigue and paleness. Additionally, chronic renal failure may cause **GI hemorrhage** due to uremic platelet dysfunction (caused by the accumulation of uremic toxins), which further worsens the anemia and contributes to fatigue and paleness.
1100
Why does uremia cause medullary suppression in chronic renal failure?
Uremia is a buildup of waste products in the blood. It causes medullary suppression in chronic renal failure due to **toxic effects of uremic toxins on the bone marrow**.
1101
What are the possible sodium imbalances in chronic renal failure?
Hyponatremia or Hypernatremia, due to impaired sodium regulation by the kidneys.
1102
Why does chronic renal failure often lead to hyperkalemia?
Due to decreased renal potassium excretion, as the kidneys are less able to filter and excrete potassium properly.
1103
Why does chronic renal failure cause metabolic acidosis?
The kidneys' reduced ability to excrete hydrogen ions (H⁺) and reabsorb bicarbonate (HCO₃⁻) results in an accumulation of acids in the body.
1104
Why does chronic renal failure lead to osteodystrophy?
Chronic renal failure leads to **decreased active vitamin D production** due to impaired kidney function. This causes **hypocalcemia**, which triggers secondary hyperparathyroidism (high PTH levels). The increased PTH causes bone resorption, while the lack of vitamin D impairs bone mineralization, leading to **osteodystrophy** (bone abnormalities).
1105
How does uremia lead to immune suppression in chronic renal failure?
Uremia (accumulation of waste products in the blood) causes leukocyte suppression due to uremic toxins, particularly affecting lymphocytes. This suppression leads to impaired immune response, making the body more susceptible to infections and diseases.
1106
How does chronic renal failure affect pregnancy and fertility?
Chronic renal failure (CRF) can disrupt hormonal regulation due to decreased glomerular filtration rate (GFR), leading to:
* Pregnancy: Reduced GFR increases prolactin, endorphins, and leptin levels, which suppress GnRH (gonadotropin-releasing hormone) production. This suppression results in **reduced estrogen levels**, causing amenorrhea (absence of menstruation) and increasing the risk of pregnancy interruption.
* Fertility: Similar hormonal changes (e.g., increased prolactin and reduced GnRH) lead to **decreased testosterone levels**, causing impotence and oligospermia (low sperm count), which can result in sexual dysfunction and infertility.
1107
Why does diabetes mellitus often stabilizes or appears to improve in chronic renal failure?
Chronic renal failure results in reduced renal degradation of insulin. This leads to higher plasma insulin levels. As a result, insulin’s effectiveness in controlling blood sugar increases, which may stabilize diabetes mellitus.
1108
What are the cardiovascular manifestations of chronic renal failure?
* Uremic pericarditis (due to uremia)
* Congestive heart failure and/or pulmonary edema (due to blood volume overload)
1109
What central nervous system symptoms can occur in chronic renal failure?
* Sleep disturbances
* Difficulty concentrating
* Memory loss
1110
What are the peripheral nervous system-related symptoms in chronic renal failure?
* Neuromuscular irritability
* Peripheral neuropathy
* Asterixis, myoclonus, seizures, coma (in advanced uremia)
1111
What gastrointestinal symptoms are seen in chronic renal failure?
* Peptic ulcers (due to secondary hyperparathyroidism)
* Nausea and vomiting
* Gastroenteritis
* Anorexia
* Diverticulitis
* Uremic fetor (urine-like breath odor)
* Hiccups
1112
What skin symptoms are associated with chronic renal failure?
* Pallor/paleness (due to anemia)
* Hyperpigmentation
* Easy bruising (ecchymosis)
* Transfusion-induced hemochromatosis (excess iron absorption)
* Pruritus (calcium/phosphate deposition)
* Uremic frost (crystallized urea on skin)
1113
What are the two main types of dialysis?
* **Hemodialysis**: Uses a machine to filter blood outside the body.
* **Peritoneal dialysis**: Uses the body's natural lining to filter blood inside the body (permanent access).
1114
Where is the liver located in the body?
It is located in the right upper quadrant of the abdomen.
1115
How can the liver be divided, in order to help locate pathologies?
Considering the vena cava, it can be separated into **two lobes**: right and left.
Considering the portal vein, it can be separated into **four sectors**: right posterior, right anterior, left medial and left lateral.
Finally, it can also be further subdivided into **eight segments**.
1116
What are the four major functions of the liver?
1. Energy metabolism and substrate interconversion
2. Protein synthesis
3. Solubilization, transport and storage
4. Protection and clearance
1117
The liver is a major intervenient in the synthesis, metabolism and interconversion of three organic compounds. Name them.
Carbohydrates, lipids and proteins.
1118
How does the liver increase glucose consumption?
Essentially, by two mechanisms:
* Storing glucose in the liver as glycogen (through glycogenesis);
* Promoting the synthesis of fatty acids and
cholesterol (through glycolysis to generate acetyl-CoA).
1119
When there is an increase of the insulin:glucagon ratio, the liver ________ (increases/decreases) insulin consumption.
increases
1120
A decrease in blood glucose levels results in a ____________ (increase/decrease) in insulin:glucagon ratio in the blood.
decrease
1121
Where are cholesterol and very-low-density lipoproteins (VLDL) stored?
In adipocytes (adipose tissue).
1122
How are fatty acids produced from glucose?
First, glucose is converted into acetyl-CoA (acetyl coenzyme A), through glycolysis. Then, acetyl-CoA is converted into fatty acids through the fatty acid synthesis process.
1123
How are fatty acids converted into triglycerides?
After being synthetized in the liver, fatty acids are esterified to glycerol to form triglycerides.
1124
What is the function of very-low-density lipoproteins (VLDL)?
The main function of very-low-density lipoproteins is to transport triglycerides and cholesterol to adipocytes.
1125
Why are triglycerides and cholesterol stored in adipocytes?
To serve as a source of energy for different tissues (such as muscles).
1126
In the liver, cholesterol can be catabolized to ________________.
bile acids
1127
How does the liver increase glucose production?
Essentially, by three mechanisms:
* Converting stored glygogen into glucose, through **glycogenolysis**.
* Converting the triglycerides stored in adipocytes into fatty acids, to be transported to the liver and synthetize **ketone bodies**, used for energy in the brain and muscles.
* Degrading proteins from muscles into aminoacids in order to be transported into the liver to produce glucose through **gluconeogenesis**.
1128
The production of glucose from aminoacids is called ____________ (gluconeogenesis/glycogenolysis).
gluconeogenesis
1129
What is glycogenolysis?
The process of conversion of glycogen stored in the liver into glucose.
1130
In the liver, there are three major processes occur related to lipids. Name them.
* Lipid acquisition
* Lipid storage
* Lipid consumption
1131
How can lipids be acquired by the liver through dietary fat?
1. Dietary fats (mainly triglycerides) are digested in the small intestine, where they are emulsified by bile salts and broken down by lipases (pancreatic enzymes).
2. The resulting products are absorbed by the intestine and stored in chylomicrons (lipoproteins).
3. Chylomicrons enter the blood, where they are hydrolysed by lipoprotein lipase, losing triglycerides (which are taken by the tissues).
4. After losing triglycerides, the chylomicron remnants (including cholesterol and fatty acids) are taken up by the liver via endocytosis.
1132
How can lipids (triglycerides and cholesterol) be acquired by the liver through VLDL and HDL?
Triglycerides and cholesterol stored in adipose tissue or found in the bloodstream can return to the liver by endocytosis of very-low-density lipoproteins (VLDL) and high-density proteins (HDL).
1133
How can lipids be acquired by the liver through glycolysis?
When there is an excess of glucose, it is converted into acetyl-CoA through glycolysis, in the liver. Then, acetyl-CoA stimulates the production of fatty acids, triglycerides and cholesterol.
1134
How can fatty acids be stored in the liver?
In the liver, fatty acids can be stored within lipid droplets or can led to the synthesis of triglycerides.
1135
What is the role of high-density proteins (HDL) in the lipid metabolism?
They collect cholesterol from the tissues and blood and return it to the liver.
| Psst! That's why it is called good cholesterol :)
1136
What is the main source of the body's cholesterol?
Endogenous synthesis in the liver (~80% of total cholesterol), from acetyl-CoA, mainly when there is an excess of glucose.
1137
Which lipids predominate in chylomicron remnants?
Cholesterol, fatty acids and small amounts of triglycerides.
1138
How are fatty acids stored in the liver?
Once in the liver, fatty acids are converted into triglycerides and stored within lipid droplets (triglyceride core with a phospholipidic monolayer containing some structural proteins around it).
1139
What is lipolysis in the liver?
Lipolysis is the hydrolysis of triglycerides into glycerol and fatty acids.
1140
What are the two products of lipolysis?
Glycerol and free fatty acids.
1141
What is β-oxidation and where does it occur?
β-oxidation is the metabolic process by which fatty acids are oxidized to produce energy. It occurs in the mitochondria and peroxisomes.
1142
What is the main purpose of β-oxidation?
Energy production.
1143
How are triglycerides and cholesterol transported to other tissues?
They are packaged into very-low-density lipoproteins (VLDL) and secreted into the bloodstream.
1144
How is cholesterol excreted by the liver?
Cholesterol can be transported by VLDL to other tissues or secreted into bile.
1145
The liver is is known for the production and secretion of several proteins. Name some of them.
* Albumin.
* Clotting factors.
* Angiotensinogen.
* Insulin-like growth factor I.
* Apolipoproteins
* Thyroid-hormone-binding globulin
* Transferrin and ferritin
1146
What is bile and what is its main function?
Bile is a "detergent-like" substance produced by the liver that facilitates the emulsification and solubilization of lipids in the aqueous environment of the intestine, aiding in lipid digestion and absorption.
1147
Which types of substances are solubilized by bile that would otherwise be insoluble?
Hydrophobic substances, such as lipids.
1148
What is the enterohepatic circulation of bile?
It is the recycling pathway where bile acids are secreted into the intestine, reabsorbed in the ileum, and returned to the liver via the portal circulation.
1149
What is the first step of enterohepatic circulation?
Bile is synthesized by hepatocytes and transported into the biliary tract.
1150
What happens to bile once it reaches the duodenum?
Bile acids promote lipid emulsification, allowing for efficient digestion and absorption of dietary fats.
1151
In which part of the gastrointestinal tract are bile acids primarily reabsorbed?
The ileum.
1152
How do bile acids return to the liver?
By reentering the portal blood flow.
1153
How does the liver contribute to the excretion of drugs and toxic substances?
Some drugs or toxic substances (including cholesterol and bilirubin) that enter the liver via portal vein are hydrophobic, being difficult to excrete. Thus, the liver present some enzymes able to catalyze metabolic reactions that make those substances more hydrophilic, helping their solubilization and excretion.
1154
Where is vitamin A stored?
Vitamin A is stored in lipid droplets that can be found in lipocytes.
1155
Half of the ________ concentration found in the human body is stored in the liver.
folate
1156
What is the importance of the ammonia metabolism in the liver?
The metabolism of proteins and aminoacids in the liver results in the production of ammonia which is toxic for the cells.
Thus, within the hepatocytes, ammonia is converted into urea, a much less toxic substance that is excreted by the kidneys through urine.
1157
Name the 5 main hepatic biomarkers.
* Alanine transaminase (ALT) or glutamic pyruvic transaminase (GPT)
* Aspartate aminotransferase (AST) or
glutamic-oxaloacetic transaminase (GOT)
* Gamma-glutamyl transferase (γ-GT)
* Alkaline phosphatase (ALP)
* Bilirubin
1158
What can elevated levels of γ-GT in the blood indicate?
High levels of γ-GT can indicate bile duct blockage or constriction, or other liver damage, since they are produced for cellular protection and detoxication.
1159
How is bilirubin produced?
Bilirubin is produced by the degradation of hemoglobin, during hemolysis.
1160
Bilirubin can exist in two forms. The unconjugated (or indirect) form is found in the ____________ (intestine/blood), while the conjugated (or direct) form is found in the ____________ (intestine/blood).
blood, intestine
1161
Where is unconjugated bilirubin converted into conjugated bilirubin?
In hepatocytes, in the liver.
1162
How can bilirubin enter the liver?
By binding to albumin in the blood.
1163
What do elevated levels of bilirubin indicate?
Elevated levels of bilirubin appear in case of hepatocellular injury, hemolysis, or bile duct obstruction.
1164
How is bilirubin transported from the liver into the intestine?
It is excreted in the bile.
1165
Besides the main biomarkers, name other parameters that can also be used to assess liver function.
* Albumin (the liver is responsible for protein synthesis)
* Total serum protein (the liver is responsible for protein synthesis)
* Lactate dehydrogenase (LDH) (enzyme released when there is cell damage, not specific to the liver)
* Prothrombin time (PT) (the liver is responsible for coagulation factor synthesis)
1166
What are the two grading systems used for liver functions?
Modified Child-Turcotte-Pugh score and Model for End-Stage Liver Disease
1167
What are the three main categories of liver diseases?
* Infectious and immune disorders
* Toxic and metabolic disorders
* Structural and neoplastic disorders
1168
Name some infectious and immune hepatic disorders.
* Viral hepatitis
* Autoimmune hepatitis
* Cholangitis
1169
Name some toxic and metabolic hepatic disorders.
* Wilson's disease (abnormal accumulation of copper)
* Hemochromatosis (abnormal accumulation of iron)
* Alcoholic liver disease (steatosis, hepatitis, cirrhosis)
* Drug-induced (e.g., ibuprofen and paracetamol) liver injury
* Non-alcoholic fatty liver disease (fibrosis, steatosis, non-alcoholic steatohepatitis, cirrhosis)
1170
Name some structural and neoplastic hepatic disorders.
* Cysts
* Cholestasis
* Hepatic benign tumors
* Hepatocellular carcinoma
* Liver cirrhosis
1171
What can liver diseases cause hypoglicemia?
When the hepatocytes lose their function or there is a lost of hepatocytes, they might not be able to produce glucose from carbohydrate metabolism.
1172
What can liver diseases cause hyperglicemia?
When the glucose in circulation can’t be cleared by hepatocytes, especially when there is a portal-to-systemic shunting (direct communication between the hepatic artery and the portal vein).
1173
What are four possible complications of fat accumulation?
* Appearance of xanthomas (subcutaneous accumulations of cholesterol)
* Obesity
* Fatty liver disease (accumulation of fat in the liver with no signs of liver damage)
* Steatohepatitis (accumulation of fat in the
liver that already caused inflammation and
liver cell damage)
1174
What is hepatic encephalopathy and what causes it?
When the normal function of the liver is compromised, the production and clearance of some essential proteins is deregulated, which affects the clearance of toxins.
Hepatic encephalopathy is a brain dysfunction due to liver dysfunction. It happens when certain toxins such as the ammonia accumulate in the blood, having a hazardous effect over the normal central nervous system function.
1175
What are the two main complications of impaired bile secretion?
* Malabsorption of lipids and lipid-based vitamins (e.g., vitamins A and D), because they cannot be solubilized;
* Jaundice, which is the accumulation of bilirubin in circulation because it cannot be solubilized.
1176
What are the three main types/causes of jaundice?
* Hemolytic (accumulation of bilirubin due to increased hemolysis)
* Hepatocellular (damaged hepatocytes)
* Obstructive (impaired excretion)
1177
What causes hypercholesteremia?
It happens when:
* LDL can’t re-enter the liver, due to misfunction of LDL receptors, for instance);
* LDL cholesterol can not be cleared from the bloodstream, due to some impairment in the lipid metabolism.
1178
What is one possible complication of hypercholesteremia?
Atherosclerosis
1179
What is hepatitis?
Consists in an inflammation of the liver, which might result in liver cells death by necrosis or apoptosis.
1180
What are the two main types of hepatitis?
* Infectious hepatitis
* Toxic hepatitis
1181
What are the three types of infectious hepatitis?
* Viral hepatitis
* Bacterial hepatitis
* Parasitic hepatitis
1182
What are the three types of toxic hepatitis?
* Alcoholic hepatitis
* Drug hepatitis
* Chemical hepatitis
1183
Besides infectious and toxic hepatitis, what are the other three possible types of hepatitis?
* Radiation hepatitis
* Autoimmune hepatitis
* Genetic hepatitis
1184
Name the 5 types of viral hepatitis.
* Hepatitis A
* Hepatitis B
* Hepatitis C
* Hepatitis D
* Hepatitis E
1185
Which types of viral hepatitis have preventive vaccination?
Hepatitis A and Hepatitis B
1186
What is the particularity of hepatitis D regarding infection?
Hepatitis D can only infect if the person has already been infected with hepatitis B.
1187
T/F: Hepatitis B vaccination protects against hepatitis D.
**True.** Because Hepatitis D recquires previous infection by Hepatitis B.
1188
T/F: Hepatitis is described as a chronic inflammation.
**False.** It can present both as an acute/short-term condition and as a chronic condition (> 6 months).
1189
What triggers the inflammation process in viral hepatitis?
First, there is an infection with a virus that targets the liver, such as hepatitis A, B, C, D or E. The virus invades hepatocytes and damages them. The immune system is activated due to the presence of foreign particles and to the damaged tissue, starting the inflammation process.
1190
Regarding incubation, refer for each of the following items which types of viral hepatitis are:
a) short-term
b) medium-term
c) long-term
a) hepatitis A and hepatitis E
b) hepatitis D
c) hepatitis B and hepatitis C
1191
Name some drugs that might have toxic effects on liver cells.
* Diclofenac (voltaren)
* Acetylsalicylic acid (aspirin)
* Tamoxifen (chemotherapy drug used in breast cancer treatment)
* Methotrexate (common treatment in autoimmune disorders and some types of cancer)
* Amoxicillin-clavulanate (large spectrum antibiotic)
* Nicotinic acid
* Cocaine
1192
How does alcohol intake lead to the production of NADH (coenzyme)?
The ethanol present in alcohol is converted into acetaldehyde, generating NADH. Then, acetaldehyde is converted into acetate, generating more NADH.
1193
How does chronic alcohol intake lead to impaired gluconeogenesis and what are the consequences on blood glucose levels?
The ethanol present in alcohol is converted into acetaldehyde, generating NADH. Then, acetaldehyde is converted into acetate, generating more NADH.
The excess of NADH levels leads to the conversion of pyruvate into lactate (then resulting in glycolysis), instead of converting lactate into pyruvate (which then would allow glyconeogenesis).
Pyruvate + NADH ⇌ Lactate + NAD+
Since gluconeogenesis is impaired, then there is a decreased glucose production, leading to hypoglycemia.
1194
How does chronic alcohol intake cause lactic acidemia?
Ethanol leads to the excess production of NADH, which causes pyruvate to te converted into lactate (instead of the other way around).
The increased lactate production in turn results in
excessive lactate delivery to the blood and a
consequent lactic acidemia.
1195
How does chronic alcohol intake lead to hyperlipidemia?
Ethanol is converted into acetaldehyde, which is then converted into acetate. So, excess ethanol leads to excess acetate.
On one hand, the excess acetate is converted to acetyl-CoA, which promotes fatty acid *de novo* synthesis. ⇒ **More production of fatty acids** ⇒ **More lipids**
On the other hand, it leads to impaired fatty acid β-oxidation (which converts fatty acids into acetyl-CoA, then used for ATP production). ⇒ **Less breakdown of fatty acids** ⇒ **More lipids**
Excess fatty acids lead to an increased triglyceride and VLDL production. ⇒ **More lipids**
Therefore, the increased lipid production leads to increased lipid blood levels, causing hyperlipidemia.
1196
Why does chronic alcohol intake lead to mitochondrial oxidative stress and how does it affect hepatocytes?
Excess ethanol results in excess mitochondrial NADH production, which consequently results in excess reactive oxygen species (ROS) production. This causes mitochondrial stress leading to the triggering of the mitochondrial apoptosis pathway and hepatocyte death.
1197
What are the three most important general pathophysiological effects of alcohol consumption on the liver?
* Disorganizes the lipid portion of cell membranes, leading to adaptative changes in their composition;
* Alters the capacity of liver cells to cope with environmental toxins (due to altered permeability);
* Oxidation of ethanol produces acetaldehyde, a toxic and reactive intermediate.
1198
Name some of the clinical manifestations of acute hepatitis.
General inflammation symptoms:
* muscle and joint pain
* fever
* feeling and being sick
* fatigue
* nausea
* loss of appetite
More specific symptoms:
* abdominal pain
* dark urine
* grey-colored stool
* itchy skin
* jaundice
1199
Name the additional clinical manifestations that normally appear in chronic hepatitis (compared to acute hepatitis).
* swelled legs, ankles and feet
* blood loss in stool and vomit
* confusion/disorientation
1200
Name the 4 stages of liver disease in hepatitis.
1. Acute hepatitis
2. Chronic hepatitis
3. Cirrhosis
4. Liver cancer
1201
What are the three main imaging techniques used for the diagnosis of hepatitis?
* Ultrasound (evaluate liver size, texture, biliary tract, and rule out constriction/obstruction)
* Elastography (to assess the tissue stiffness and check for scarring, i.e., fibrosis)
* Computed Tomography
1202
What are the main biochemical blood tests used to diagnose hepatitis?
* **Liver function tests** (ALT, AST, γ-GT, ALP, bilirubin, albumin, etc…)
* **Serological tests** (anti-HAV, anti-HBV, anti-HCV, anti-HDV, anti-HEV, etc…) - to check if it is viral hepatitis.
* **Autoimmune screenings** (ANA, IgG levels, etc…) - to check if it is autoimmune hepatitis.
* **Toxicologic and/or metabolic screenings** (drug levels, ferritin, transferrin, etc...) - to check if it is toxic hepatitis (caused by alcohol, drugs or chemicals).
1203
What is cholestasis?
It's the impairment of bile secretion or flow in consequence of intrahepatic or extrahepatic
conditions.
1204
What are the main clinical manifestations of cholestasis?
* Jaundice
* Dark urine and light-colored stools containing fat (steatorrhea)
* Pruritus
* Malabsorption of fat and fat soluble vitamins (e.g. D vitamin)
1205
What are the main causes of intrahepatic cholestasis?
* Acute hepatitis
* Medication
* Pregnancy
* Primary biliary cholangitis
* Primary sclerosing cholangitis
1206
What are the main causes of extrahepatic cholestasis?
* Obstructing gallstone
* Carcinoma of the bile duct
* Carcinoma of the head of the pancreas
* Bile duct strictures
* Primary sclerosing cholangitis
1207
What are the main biochemical blood tests done to diagnose cholestasis?
* Liver function tests (ALT, AST, γ-GT, ALP, bilirubin, albumin, etc…)
* Toxicologic and/or metabolic screenings (drug levels, ferritin, transferrin,
etc...)
1208
What are the expected results of biochemical blood tests in the case of cholestasis?
* Increased concentrations of serum alkaline phosphatase, γ-GT and bilirubin.
* Possibly, increased cholesterol levels (due
to poor excretion).
1209
What are the main imaging techniques used to diagnose cholestasis?
* **Ultrasound** (to assess bile duct dilation or the presence of stones or masses)
* **Computed Tomography**
* **Endoscopic retrograde cholangiopancreatography** (X-ray imaging acquired after injection of a contrast agent through a endoscopy tube inserted through the mouth and into the small intestine. It is used when there’s a suspicion of a blockage in the bile ducts.)
* **Magnetic resonance cholangiopancreatography**
(specific MRI to observe bile and pancreatic ducts)
1210
How can biopsy help to diagnose cholestasis?
It can be used in unclear cases or to assess intrahepatic causes.
1211
How can biopsy help in the diagnosis of hepatitis?
It can be used in unclear cases or to assess severity and fibrosis.
1212
What is non-alcoholic
fatty liver disease?
Fat accumulation in the liver (steatosis), which can range from absent or minimal inflammation of hepatocytes (fatty liver or steatosis) up to a condition in which there are already some liver inflammation (non-alcoholic steatohepatitis).
1213
T/F: Fatty liver is a reversible condition.
True.
1214
Name some of the causes of non-alcoholic fatty liver disease.
* Obesity
* High cholesterol
* High triglycerides
* Genetic predisposition
* Type 2 diabetes
* Insulin resistance
1215
What happens if non-alcoholic fatty liver disease progresses? What are the next stages?
It can lead to non-alcoholic steatohepatitis, cirrhosis and, finally, hepatocellular carcinoma.
1216
T/F: Non-alcoholic fatty liver disease is characterized by inflammation and steatosis.
**False.** In non-alcoholic fatty liver disease, there is no inflammation, only steatosis (presence of fat in hepatocytes).
1217
Explain the development of fibrosis in the progression of non-alcoholic fatty liver disease.
The excess accummulation of fat in hepatocytes is lipotoxic and damages these cells.
In response to the liver cells damage, the liver attempts to repair itself and replace damaged cells, leading to inflammation and deposition collagen and other extracellular matrix components, formim a high density matrix.
This leads to the formation of scar tissue, especially when there are repeated or continuous
injuries, resulting in fibrosis.
1218
What are the main symptoms of early-stage cirrhosis?
General inflammation symptoms, such as:
* tiredness and weakness
* nausea
* loss of appetite
* loss of weight and muscle mass
1219
Is cirrhosis reversible? Why?
**No.** In cirrhosis, the normal architecture of the liver is irreversibly altered, and the scar tissue replaced normal functioning tissue, compromising the liver function.
1220
What are the main symptoms of advanced cirrhosis?
* itchiness (probably due to the accumulation of toxic substances as a result of liver dysfunction)
* lower limb edema
* ascites (fluid accumulation in the abdomen)
* jaundice
* red patches on the palms and small, spider-like blood vessels on the skin (spider angiomas) above waist level
1221
What are the main complications of cirrhosis?
* Hepatic encephalopathy
* Bleeding from the GI tract
* Liver cancer
